Pyrrolopyridine derivatives substituted with cyclic amino group

ABSTRACT

An object of the present invention is to provide an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer&#39;s disease, Parkinson&#39;s disease, Huntington&#39;s chorea, eating disorder, hypertension, gastric diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc. This problem can be solved with a pyrrolopyrimidine or pyrrolopyridine derivative substituted with a cyclic amino group represented by formula [I] below which has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

This is a divisional of application Ser. No. 12/106,873 filed Apr. 21,2008, which is a continuation of application Ser. No. 10/504,981 filedMay 16, 2005, which is a National Stage Application of InternationalApplication No. PCT/JP2003/16598 filed Dec. 24, 2003, which claimspriority to Japanese Patent Application No. 2002-383667 filed Dec. 26,2002. The entire disclosures of the prior applications are consideredpart of the disclosure of the accompanying divisional application andare hereby incorporated by reference.

DETAILED DESCRIPTION OF THE INVENTION

1. Technical Field

The present invention relates to a therapeutic agent for diseases inwhich corticotropin releasing factor (CRF) is considered to be involved,such as depression, anxiety, Alzheimer's disease, Parkinson's disease,Huntington's chorea, eating disorder, hypertension, gastral diseases,drug dependence, cerebral infarction, cerebral ischemia, cerebral edema,cephalic external wound, inflammation immunity-related diseases,alpecia, irritable bowel syndrome, sleep disorders, epilepsy,dermatitides, schizophrenia, etc.

2. Description of the Prior Art

CRF is a hormone comprising 41 amino acids (Science, 213, 1394-1397,1981; and J. Neurosci., 7, 88-100, 1987), and it is suggested that CRFplays a core role in biological reactions against stresses (Cell. Mol.Neurobiol., 14, 579-588, 1994; Endocrinol., 132, 723-728, 1994; andNeuroendocrinol. 61, 445-452, 1995). For CRF, there are the followingtwo paths: a path by which CRF acts on peripheral immune system orsympathetic nervous system through hypothalamus-pituitary-adrenalsystem, and a path by which CRF functions as a neurotransmitter incentral nervous system (in Corticotropin Releasing Factor: Basic andClinical Studies of a Neuropeptide, pp. 29-52, 1990). Intraventricularadministration of CRF to hypophysectomized rats and normal rats causesan anxiety-like symptom in both types of rats (Pharmacol. Rev., 43,425-473, 1991; and Brain Res. Rev., 15, 71-100, 1990). That is, thereare suggested the participation of CRF in hypothalamus-pituitary-adrenalsystem and the pathway by which CRF functions as a neurotransmitter incentral nervous system.

The review by Owens and Nemeroff in 1991 summarizes diseases in whichCRF is involved (Pharmacol. Rev., 43, 425-474, 1991). That is, CRF isinvolved in depression, anxiety, Alzheimer's disease, Parkinson'sdisease, Huntington's chorea, eating disorder, hypertension,gastrointestinal diseases, drug dependence, inflammation,immunity-related diseases, etc. It has recently been reported that CRFis involved also in epilepsy, cerebral infarction, cerebral ischemia,cerebral edema, and cephalic external wound (Brain Res. 545, 339-342,1991; Ann. Neurol. 31, 48-498, 1992; Dev. Brain Res. 91, 245-251, 1996;and Brain Res. 744, 166-170, 1997). Accordingly, antagonists against CRFreceptors are useful as therapeutic agents for the diseases describedabove.

WO02/002549 and WO00/053604 disclose pyrrolopyridine andpyrrolopyrimidine derivatives respectively as CRF receptor antagonists.Bioorganic & Medicinal Chemistry 10 (2002) 175-183 also disclosespyrrolopyrimidine derivatives. However, none disclose the compoundsprovided in the present invention.

Problem(s) to be Solved by Invention

An object of the present invention is to provide an antagonist againstCRF receptors which is effective as a therapeutic or prophylactic agentfor diseases in which CRF is considered to be involved, such asdepression, anxiety, Alzheimer's disease, Parkinson's disease,Huntington's chorea, eating disorder, hypertension, gastral diseases,drug dependence, epilepsy, cerebral infarction, cerebral ischemia,cerebral edema, cephalic external wound, inflammation, immunity-relateddiseases, alpecia, irritable bowel syndrome, sleep disorders, epilepsy,dermatitides, schizophrenia, etc.

Means for Solving Problem

The present inventors earnestly investigated pyrrolopyrimidine andpyrrolopyridine derivatives substituted with a cyclic amino group thathave a high affinity for CRF receptors, whereby the present inventionhas been accomplished.

The present invention is pyrrolopyrimidine and pyrrolopyridinederivatives substituted with a cyclic amino group explained below.

A pyrrolopyrimidine or pyrrolopyridine derivative substituted with acyclic amino group represented by the following formula [I]:

(wherein the cyclic amino group is represented by the following formula[II]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—X, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;

X is cyano, hydroxy or —OR⁹;

Y is N or CR¹⁰;

R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

R² is hydrogen or C₁₋₅alkyl;

R³ is hydrogen, cyano, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

m is an integer selected from 0, 1, 2, 3, 4 and 5;

n is 0 or 1;

with the proviso that when X is hydroxy or OR⁹, and n is 0, then m is aninteger selected from 1, 2, 3, 4 and 5;

R⁴ is hydrogen, hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl orC₁₋₅alkyl;

R⁵ is hydrogen or C₁₋₅alkyl;

R⁶ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy or —N(R¹¹)R¹²;

R⁷ and R⁸ are the same or different, and independently are hydrogen,halogen, C₁₋₅ alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅ alkyl, hydroxy,C₁₋₅ alkoxy, C₃₋₈cycloalkyloxy, —N(R^(11a))R^(12a), —CO₂R¹³, cyano,nitro, C₁₋₅alkylthio, trifluoromethyl or trifluoromethoxy; or R⁷ and R⁸are taken together to form —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—;

R⁹ is C₁₋₂₄acyl, C₁₋₁₀alkoxycarbonyl, aryl-C₁₋₅alkyloxycarbonyl,—CO—O—CHR¹⁴—O—CO—R¹⁵, —P(═O)(OR^(14a))OR^(15a),—CO—(CH₂)_(p)—(CHR¹⁶)_(q)—NR¹⁷R¹⁸, arylcarbonyl or heteroarylcarbonyl,wherein each said acyl, aryl and heteroaryl is unsubstituted orsubstituted with C₁₋₅alkoxy, and C₁₋₂₄acyl optionally includes one tosix double bonds;

R¹⁰ is hydrogen, C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹;

Ar is aryl or heteroaryl which aryl or heteroaryl is unsubstituted orsubstituted with 1 or more substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio,C₁₋₅alkylsulfinyl, C₁₋₅alkylsulfonyl, cyano, nitro, hydroxy,—CO₂R^(19a); —C(═O)R^(19a); —CONR^(11b)R^(12b), —OC(═O)R^(19a),—NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹; with the proviso that when X is hydroxy, Y is N, and thecyclic amino group is 5-membered ring, then Ar is aryl or heteroarylwhich aryl or heteroaryl is substituted with at least one ofsubstituents which are selected from halogen and trifluoromethyl;

R¹¹ and R¹² are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11a) and R^(12a) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11b) and R^(12b) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R¹³ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,C₁₋₅alkoxy-C₁₋₅alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl;

R¹⁴ and R¹⁵ are the same or different, and independently are hydrogen,C₁₋₅alkyl or aryl-C₁₋₅alkyl;

R^(14a) and R^(15a) are the same or different, and independently arehydrogen, C₁₋₅alkyl or aryl-C₁₋₅alkyl;

R¹⁶ is hydrogen, C₁₋₅alkyl, aryl, heteroaryl, aryl-C₁₋₅alkyl,heteroaryl-C₁₋₅alkyl, hydroxy-C₁₋₅alkyl, hydroxycarbonyl-C₁₋₅alkyl,hydroxyphenyl-C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl, amino-C₁₋₅alkyl,guanidino-C₁₋₅alkyl, mercapto-C₁₋₅alkyl, C₁₋₅alkylthio-C₁₋₅alkyl oraminocarbonyl-C₁₋₅alkyl;

R¹⁷ and R¹⁸ are the same or different, and independently are hydrogen,

C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, C₁₋₁₀acyl,C₁₋₁₀alkoxycarbonyl or aryl-C₁₋₅alkyloxycarbonyl;

or R¹⁶ and R¹⁷ are taken together to form —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂—or —CH₂CH₂CH₂CH₂—;

p is an integer selected from 0, 1, 2, 3, 4 and 5;

q is 0 or 1;

R¹⁹ is hydrogen or C₁₋₅alkyl;

R^(19a) is hydrogen or C₁₋₅alkyl;

r is 1 or 2;

R²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₅alkyl), individual isomers thereof, racemic or non-racemic mixturesof isomers thereof or N-oxide thereof, or pharmaceutically acceptablesalts and hydrates thereof.

The terms used in the present specification have the following meanings.

The term “a 3- to 8-membered saturated cyclic amine” means aziridine,azetidine, pyrrolidine, piperidine, azepane or azocane.

The term “C₁₋₅alkylene” means a straight or branched chain alkylene of 1to 5 carbon atoms, such as methylene, ethylene, propylene, trimethylene,tetramethylene, pentamethylene or the like.

The term “a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine” includes, for example,8-azabicyclo[3.2.1]oct-8-yl, 9-azabicyclo[3.3.1]non-9-yl,7-azabicyclo[2.2.1]hept-7-yl, 3-oxa-7-azabicyclo[3.3.1]non-7-yl and3-oxa-9-azabicyclo[3.3.1]non-9-yl.

The term “C₁₋₅alkyl” means a straight chain or branched chain alkylgroup of 1 to 5 carbon atoms, such as methyl, ethyl, propyl, isopropyl,butyl, isobutyl, t-butyl, sec-butyl, pentyl, isopentyl or the like.

The term “C₁₋₅alkoxy” means a straight chain or branched chain alkoxygroup of 1 to 5 carbon atoms, such as methoxy, ethoxy, propoxy,isopropyloxy, butoxy, isobutyloxy, pentyloxy, isopentyloxy or the like.

The term “C₁₋₅alkoxy-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving the above-mentioned C₁₋₅alkoxy group as the substituent, such asmethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl or the like.

The term “hydroxy-C₁₋₅alkyl” means a substituted C₁₋₅alkyl group havinghydroxy group, such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl,5-hydroxypentyl or the like.

The term “cyano-C₁₋₅ alkyl” means a substituted C₁₋₅alkyl group havingcyano group, such as cyanomethyl, 1-cyanoethyl, 2-cyanoethyl,3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl or the like.

The term “C₃₋₈cycloalkyl” means a cyclic alkyl group of 3 to 8 carbonatoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl or the like.

The term “C₃₋₈cycloalkyl-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving the above-mentioned C₃₋₈cycloalkyl as the substituent, such ascyclopropylmethyl, cyclopropylethyl, cyclopentylethyl or the like.

The term “C₃₋₈cycloalkyloxy” means a cyclic alkoxy group of 3 to 8carbon atoms, such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy orthe like.

The term “halogen” means fluorine, chlorine, bromine or iodine atom.

The term “C₃₋₈cycloalkyloxy-C₁₋₅alkyl” means a substituted C₁₋₅alkylgroup having the above mentioned C₃₋₈cycloalkyloxy as the substituent,such as cyclopropyloxymethyl, 2-cyclopropyloxyethyl or the like.

The term “C₁₋₅alkylthio” means a straight chain or branched chainalkylthio group of 1 to 5 carbon atoms, such as methylthio, ethylthio,propylthio or the like.

The term “C₁₋₂₄acyl” means a straight chain or branched chain, andsaturated or unsaturated acyl group of 1 to 24 carbon atoms, such asacetyl, propionyl, butyryl, pentanoyl, hexanoyl, heptanoyl, octanoyl,nonanoyl, decanoyl, isobutyryl, 2,2-dimethylpropionyl,octadeca-9,12-dienoyl, eicosa-5,8,11,14-tetraenoyl,docosa-4,7,10,13,16,19-hexaenoyl, eicosa-5,8,11,14,17-pentaenoyl or thelike.

The term “C₁₋₁₀alkoxycarbonyl” means a straight chain or branched chainalkoxycarbonyl group of 2 to 11 carbon atoms, such as methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl,hexyloxycarbonyl, heptyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl,decyloxycarbonyl, isopropoxycarbonyl, t-butoxycarbonyl or the like.

The term “aryl” means a monocyclic or bicyclic group of 6 to 12 ringcarbon atoms having at least one aromatic ring, such as phenyl, naphthylor the like.

The term “aryl-C₁₋₅alkyloxycarbonyl” means a substitutedC₁₋₅alkyloxycarbonyl group having the above-mentioned aryl as thesubstituent, such as benzyloxycarbonyl, phenethyloxycarbonyl or thelike.

The term “arylcarbonyl” means a substituted carbonyl group having theabove-mentioned aryl as the substituent, such as benzoyl,naphthalene-1-carbonyl, naphthalene-2-carbonyl or the like.

The term “heteroaryl” means a monocyclic or bicyclic group of 5 to 12ring atoms having at least one aromatic ring having in its ring 1 to 4atoms which may be the same or different and are selected from nitrogen,oxygen and sulfur, such as pyridyl, pyrimidinyl, imidazolyl, quinolyl,indolyl, benzofuranyl, quinoxalinyl, benzo[1,2,5]thiadiazolyl,benzo[1,2,5]oxadiazolyl or the like.

The term “heteroarylcarbonyl” means a substituted carbonyl group havingthe above-mentioned heteroaryl as the substituent, such aspyridine-2-carbonyl, pyridine-3-carbonyl, pyridine-4-carbonyl,pyrimidine-2-carbonyl, pyrimidine-4-carbonyl, pyrimidine-5-carbonyl orthe like.

The term “C₂₋₅alkenyl” means a straight chain or branched chain alkenylgroup of 2 to 5 carbon atoms, such as vinyl, isopropenyl, allyl or thelike.

The term “C₂₋₅alkynyl” means a straight chain or branched chain alkynylgroup of 2 to 5 carbon atoms, such as ethynyl, prop-1-ynyl, prop-2-ynylor the like.

The term “C₁₋₅alkysulfinyl” means a straight chain or branched chainalkylsulfinyl group of 1 to 5 carbon atoms, such as methanesulfinyl,ethanesulfinyl or the like.

The term “C₁₋₅alkysulfonyl” means a straight chain or branched chainalkylsulfonyl group of 1 to 5 carbon atoms, such as methanesulfonyl,ethanesulfonyl or the like.

The term “hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy” means a substitutedC₂₋₅alkoxy group having a hydroxy-C₂₋₅alkylamino group as thesubstituent such as 2-(2-hydroxyethylamino)ethoxy or the like.

The term “aryl-C₁₋₅alkyl” means a substituted C₁₋₅alkyl group having theabove-mentioned aryl as the substituent, such as benzyl, phenethyl,3-phenylpropyl, naphthalen-1-ylmethyl, naphthalen-2-ylmethyl or thelike.

The term “heteroaryl-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving the above-mentioned heteroaryl as the substituent, such as1H-indol-3-ylmethyl, 1H-imidazol-4-ylmethyl or the like.

The term “hydroxycarbonyl-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving a hydroxycarbonyl group as the substituent, such ashydroxycarbonylmethyl, 2-hydroxycarbonylethyl, 3-hydroxycarbonylpropyl,4-hydroxycarbonylbutyl or the like.

The term “hydroxyphenyl-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving a hydroxyphenyl group as the substituent, such as4-hydroxybenzyl, 3-hydroxybenzyl 2-hydroxybenzyl,2-(4-hydroxyphenyl)ethyl or the like.

The term “amino-C₁₋₅alkyl” means a substituted C₁₋₅alkyl group having aamino group as the substituent, such as aminomethyl, 1-aminoethyl,2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl or the like.

The term “guanidino-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving a guanidino group as the substituent, such as guanidinomethyl,1-guanidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl,5-guanidinopentyl or the like.

The term “mercapto-C₁₋₅alkyl” means a substituted C₁₋₅alkyl group havinga mercapto group as the substituent, such as mercaptomethyl,1-mercaptoethyl, 2-mercaptoethyl, 3-mercaptopropyl, 4-mercaptobutyl,5-mercaptopentyl or the like.

The term “C₁₋₅alkylthio-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving the above-mentioned C₁₋₅alkylthio group as the substituent, suchas methylthiomethyl, 1-methylthioethyl, 2-methylthioethyl,3-methylthiopropyl, 4-methylthiobutyl, 5-methylthiopentyl or the like.

The term “aminocarbonyl-C₁₋₅alkyl” means a substituted C₁₋₅alkyl grouphaving an aminocarbonyl group as the substituent, such asaminocarbonylmethyl, 2-aminocarbonylethyl, 3-aminocarbonylpropyl,4-aminocarbonylbutyl or the like.

The phrase “aryl or heteroaryl which aryl or heteroaryl is unsubstitutedor substituted with 1 or more substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio,C₁₋₅alkylsulfinyl, C₁₋₅alkylsulfonyl, cyano, nitro, hydroxy,—CO₂R^(19a), C(═O)R^(19a), —CONR^(11b)R^(12b), —C(═O)R^(19a),—S(O)_(r)NR^(11b)R^(12b), hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy,trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy,methylenedioxy, ethylenedioxy and —N(R²⁰R²¹” includes, for example,2,4-dimethylphenyl, 2,6-dimethylphenyl, 2,4-dibromophenyl,2-bromo-4-isoproylphenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl,2-chloro-4-trifluoromethylphenyl, 4-methoxy-2-methylphenyl,2-chloro-4-trifluoromethoxyphenyl, 4-isopropyl-2-methylthiophenyl,2,4,6-trimethylphenyl, 4-bromo-2,6-dimethylphenyl,4-bromo-2,6-diethylphenyl, 4-chloro-2,6-dimethylphenyl,2,4,6-tribromophenyl, 2,4,5-tribromophenyl, 2,4,6-trichlorophenyl,2,4,5-trichlorophenyl, 4-bromo-2,6-dichlorophenyl,6-chloro-2,4-dibromophenyl, 2,4-dibromo-6-fluorophenyl,2,4-dibromo-6-methylphenyl, 2,4-dibromo-6-methoxyphenyl,2,4-dibromo-6-methylthiophenyl, 2,6-dibromo-4-isopropylphenyl,2,6-dibromo-4-trifluoromethylphenyl, 2-bromo-4-trifluoromethylphenyl,4-bromo-2-chlorophenyl, 2-bromo-4-chlorophenyl, 4-bromo-2-methylphenyl,4-chloro-2-methylphenyl, 2,4-dimethoxyphenyl,2,6-dimethyl-4-methoxyphenyl, 4-chloro-2,6-dibromophenyl,4-bromo-2,6-difluorophenyl, 2,6-dichloro-4-trifluoromethylphenyl,2,6-dichloro-4-trifluoromethoxyphenyl,2,6-dibromo-4-trifluoromethoxyphenyl, 2-chloro-4,6-dimethylphenyl,2-bromo-4,6-dimethoxyphenyl, 2-bromo-4-isopropyl-6-methoxyphenyl,2,4-dimethoxy-6-methylphenyl,2,6-dimethyl-4-[2-(2-hydroxyethylamino)ethoxy]phenyl,6-dimethylamino-4-methylpyridin-3-yl,2-chloro-6-trifluoromethylpyridin-3-yl,2-chloro-6-trifluoromethoxypyridin-3-yl, 2-chloro-6-methoxypyridin-3-yl,6-methoxy-2-trifluoromethylpyridin-3-yl,2-chloro-6-difluoromethylpyridin-3-yl, 6-methoxy-2-methylpyridin-3-yl,2,6-dimethoxypyridin-3-yl, 4,6-dimethyl-2-trifluoromethylpyrimidin-5-yl,2-dimethylamino-6-methylpyridin-3-yl,6-dimethylamino-2-methylpyridin-3-yl, 2,3-dihydrobenzo[1,4]dioxin-5-yland benzo[1,3]dioxol-4-yl, 5,7-dimethylbenzo[1,2,5]thiadiazol-4-yl,5,7-dimethylbenzo[1,2,5]oxadiazol-4-yl,2-isopropoxy-6-trifluoromethylpyridin-3-yl,2-methoxy-6-methylpyridin-3-yl, 2,6-dimethylpyridin-3-yl,2-bromo-6-methoxypyridin-3-yl, 2-chloro-6-dimethylaminopyridin-3-yl,2,6-dichloropyridin-3-yl, 2,4-dimethyl-6-dimethylaminopyridin-3-yl,2,4,6-trimethylpyridin-3-yl, 2,4,6-trimethylpyrimidin-5-yl,4,6-dimethyl-2-dimethylaminopyrimidin-5-yl, 5-iodo-3-methylpyridin-2-yl,3-methyl-5-methylaminopyridin-2-yl,3-dimethylamino-5-methylpyridin-2-yl,5-methyl-3-methylaminopyridin-2-yl, 3-chloro-5-methylpyridin-2-yl,3-amino-5-methylpyridin-2-yl, 5-methyl-3-nitropyridin-2-yl,5-diethylamino-3-methylpyridin-2-yl, 5-fluoro-3-methylpyridin-2-yl,5-chloro-3-methylpyridin-2-yl, 5-dimethylamino-3-methylpyridin-2-yl,5-amino-3-methylpyridin-2-yl, 3-methyl-5-nitropyridin-2-yl,3-bromo-5-methylpyridin-2-yl, 4-chloro-2,5-dimethoxyphenyl,4,5-dimethyl-2-methoxyphenyl, 5-fluoro-2,4-dimethylphenyl,2,4-dimethoxy-5-methylphenyl, 2-chloro-4-methoxy-5-methylphenyl,2-chloro-5-fluoro-4-methylphenyl, 2-bromo-4,5-dimethoxyphenyl,2-bromo-5-fluoro-4-methoxyphenyl, 2-chloro-4,5-dimethoxyphenyl,2.5-dichloro-4-methoxyphenyl, 2,4-dichloro-5-fluorophenyl,2-chloro-5-fluoro-4-methoxyphenyl, 2,4,5-trichlorophenyl,2-chloro-5-fluoro-4-methylphenyl, 5-fluoro-4-methoxy-2-methylphenyl,4,5-dimethoxy-2-methylphenyl, 5-chloro-4-methoxy-2-methylphenyl,2,4,5-trimethylphenyl, 6-methoxy-4-methylpyridin-3-yl,4-methoxy-6-methylpyridin-3-yl, 4,6-dimethylpyridin-3-yl,2-chloro-4-isopropylphenyl, 2-chloro-4-methylphenyl,4-amino-2-chlorophenyl, 2-chloro-4-dimethylcarbamoylphenyl,2-chloro-4-methylcarbamoylphenyl, 4-carbamoyl-2-chlorophenyl,2-chloro-4-methylsulfonylphenyl, 4-carboxy-2-chlorophenyl,2-chloro-4-iodophenyl, 2-bromo-4-methylthiophenyl,2-bromo-4-methylsulfinylphenyl, 2-bromo-4-dimethylaminophenyl,2-bromo-4-methylsulfonylphenyl, 2-bromo-4-cyclopentylphenyl,2-bromo-4-tert-butylphenyl, 2-bromo-4-propylphenyl,2-bromo-4-methylphenyl, 2-bromo-4-trifluoromethoxyphenyl,2-bromo-4-methoxyphenyl, 2-bromo-4-ethoxyphenyl,4-isopropyl-2-methylsulfonylphenyl, 4-cyclopentyl-2-methylthiophenyl,4-butyl-2-methylthiophenyl, 4-methoxy-2-methylthiophenyl,2-methylthio-4-propylphenyl, 2-dimethylamino-4-isopropylphenyl,2-iodo-4-isopropylphenyl, 2-fluoro-4-methylphenyl, 2,4-difluorophenyl,2-chloro-4-methoxyphenyl, 2-chloro-4-hydroxyphenyl,4-cyano-2-methoxyphenyl, 4-bromo-2-methoxyphenyl,2-methoxy-4-methylphenyl, 4-chloro-2-methoxyphenyl,2-hydroxy-4-methylphenyl, 4-fluoro-2-methoxyphenyl,2-hydroxy-4-methylphenyl, 4-cyano-2-methoxyphenyl,2-chloro-4-methylthiophenyl, 2-methoxy-4-trifluoromethylphenyl,4-isopropyl-2-methoxyphenyl, 2-chloro-4-cyanophenyl,2-chloro-4-ethoxycarbonylphenyl, 2-chloro-4-methylaminophenyl,4-cyano-2-trifluoromethylphenyl, 4-cyano-2-methylphenyl,2-methyl-4-trifluoromethoxyphenyl, 2-cyano-4-trifluoromethylphenyl,4-carboxyamino-2-trifluoromethylphenyl,4-methoxy-2-trifluoromethylphenyl, 4-fluoro-2-methylphenyl,4-hydroxy-2-methylphenyl, 4-methoxy-2-methoxycarbonylphenyl,2-ethyl-4-methoxyphenyl, 2-formyl-4-methoxyphenyl,4-chloro-2-trifluoromethylphenyl,4-dimethylamino-2-trifluoromethylphenyl,4-difluoromethoxy-2-methylphenyl, 2-cyano-4-methoxyphenyl,4-hydroxy-2-trifluoromethylphenyl, 4-isopropyl-2-trifluoromethylphenyl,4-diethylamino-2-methylphenyl, 4-fluoro-2-trifluoromethylphenyl,4-propoxy-2-trifluoromethylphenyl, 4-dimethylamino-2-methylthiophenyl,4-isopropyl-2-isopropylthiophenyl, 2-ethylthio-4-isopropylphenyl,4-methylamino-2-methylthiophenyl, 2-methylthio-4-propionylphenyl,4-acetyl-2-methylthiophenyl, 4-cyano-2-methylthiophenyl,4-methoxy-2-methylthiophenyl, 4-ethyl-2-methylthiophenyl,4-bromo-2-methylthiophenyl, 4-isopropyl-2-methylsulfinylphenyl,2,4-dimethylthiophenyl, 4,6-dimethyl-2-isopropylphenyl,4,6-dimethyl-2-isopropenylphenyl, 2-acetyl-4,6-dimethylphenyl,2,6-dimethyl-4-trifluoromethylphenyl, 2,6-dimethyl-4-isopropenylphenyl,4-acetyl-2,6-dimethylphenyl, 2,4,6-triethylphenyl,4,6-dimethyl-2-methylthiophenyl, 4,6-dimethyl-2-iodophenyl,2-fluoromethoxy-4,6-dimethylphenyl, 4,6-dimethyl-2-isopropoxyphenyl,4,6-dimethyl-2-ethoxyphenyl, 2,6-dichloro-4-ethoxyphenyl,2-bromo-4,6-dimethoxyphenyl, 2-bromo-6-hydroxy-4-methoxyphenyl,2,6-dibromo-4-ethoxyphenyl, 4-bromo-2-methoxy-6-methylphenyl,2,6-dibromo-4-methoxyphenyl, 4,6-dibromo-2-trifluoromethoxyphenyl,2,4-dibromo-6-trifluoromethylphenyl, 4-bromo-2-chloro-6-methylphenyl,4-chloro-2,6-dimethoxyphenyl, 2,4-dichloro-6-methoxyphenyl,4,6-dichloro-2-methylthiophenyl, 4,6-dichloro-2-trifluoromethylphenyl,2,6-dimethoxy-4-ethylphenyl, 4,6-dimethyl-2-methoxyphenyl,2,6-dimethoxy-4-methylphenyl, 2-chloro-6-methoxy-4-methylphenyl,4,6-dimethyl-2-ethoxyphenyl, 6-hydroxy-2,4-dimethylphenyl,4-cyano-2-methoxy-6-methylphenyl, 6-fluoro-2-methoxy-4-methylphenyl,4-acetyl-2-methoxy-6-methylphenyl, 2-chloro-4,6-dimethoxyphenyl,2,6-dimethoxy-4-ethoxyphenyl, 2,4,6-trimethoxyphenyl,4,6-dibromo-2-trifluoromethoxyphenyl,2-bromo-4-dimethylamino-6-methoxyphenyl,4-bromo-2-methoxy-6-methylphenyl, 4,6-dimethoxy-2-propoxyphenyl,4,6-dichloro-2-propoxyphenyl, 2-bromo-6-hydroxy-4-methoxyphenyl,2,4,6-trifluorophenyl, 2-bromo-6-fluoro-4-methylphenyl,4-difluoromethoxy-2,6-dimethylphenyl, 2,6-dimethyl-4-ethoxyphenyl,2,6-dimethyl-4-isopropoxyphenyl, 2,6-dimethyl-4-methylthiophenyl,2,6-dimethyl-4-methylsulfonylophenyl,2,6-dimethyl-4-methylsulfinylophenyl, 2,3-dichlorophenyl,4-methoxy-2,3-dimethylphenyl, 2-chloro-3-fluoro-4-methoxyphenyl,2,3,4-trichlorophenyl and 4-methoxy-2,5-dimethylphenyl.

The “pharmaceutically acceptable salts” in the present inventioninclude, for example, salts with an inorganic acid such as sulfuricacid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acidor the like; salts with an organic acid such as acetic acid, oxalicacid, lactic acid, tartaric acid, fumaric acid, maleic acid, citricacid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonicacid, benzoic acid, camphorsulfonic acid, ethanesulfonic acid,glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, malicacid, malonic acid, mandelic acid, galactaric acid,naphthalene-2-sulfonic acid or the like; salts with one or more metalions such as lithium ion, sodium ion, potassium ion, calcium ion,magnesium ion, zinc ion, aluminium ion or the like; salts with aminessuch as ammonia, arginine, lysine, piperazine, choline, diethylamine,4-phenylcyclohexylamine, 2-aminoethanol, benzathine or the like.

A compound of the present invention includes any isomers such asdiastereomers, enantiomers, geometricisomers and tautomeric forms. In acompound represented by formula [I], if the cyclic amino group has oneor more chiral carbons and/or if there is an axial chirality between Arand pyrrolopyrimidine (or pyrrolopyridine) ring, several stereoisomers(diastereomers or enantiomers) can exist. The compound of the presentinvention includes the individual isomers and the racemic andnon-racemic mixtures of the isomers.

Preferable examples of the compound of the present invention are asfollows.

That is, preferable are compounds represented by the following formula[III]

(wherein the cyclic amino group is represented by the following formula[IV]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—CN, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;

Y is N or CR¹⁰;

R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl or hydroxy-C₁₋₅alkyl;

R² is hydrogen or C₁₋₅alkyl;

R³ is hydrogen, cyano, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

m is an integer selected from 0, 1, 2, 3, 4 and 5;

n is 0 or 1;

R⁴ is hydrogen, hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl orC₁₋₅alkyl;

R⁵ is hydrogen or C₁₋₅alkyl;

R⁶ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,hydroxy, C₁₋₅alkoxy, C₃₋₄cycloalkyloxy or —N(R¹¹)R¹²;

R⁷ and R⁸ are the same or different, and independently are hydrogen,halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy,C₁₋₅alkoxy, C₃₋₈cycloalkyloxy, —N(R^(11a))R^(12a), —CO₂R¹³, cyano,nitro, C₁₋₅alkylthio, trifluoromethyl or trifluoromethoxy; or R⁷ and R⁸are taken together to form —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—;

R¹⁰ is hydrogen, C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹;

Ar is aryl or heteroaryl which aryl or heteroaryl is unsubstituted orsubstituted with 1 or more substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio,C₁₋₅alkylsulfinyl, C₁₋₅alkylsulfonyl, cyano, nitro, hydroxy,—CO₂R^(19a), —C(═O)R^(19a), —CONR^(11b)R^(12b), —OC(═O)R^(19a),—NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b)),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹;

R¹¹ and R¹² are the same or different, and independently are hydrogen,C₁₋₅ alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11a) and R^(12a) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11b) and R^(12b) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R¹³ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,C₁₋₅alkoxy-C₁₋₅ alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl;

R¹⁹ is hydrogen or C₁₋₅alkyl;

R^(19a) is hydrogen or C₁₋₅alkyl;

r is 1 or 2;

R²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₅alkyl). More preferable are compounds represented by the formula[III] in which Y is N. More preferable are compounds represented by theformula [III] in which Y is N; n is 0; R¹, R², R⁴ and R⁵ are hydrogen.More preferable are compounds represented by the formula [III] in whichY is N; the cyclic amino group is a 4- to 7-membered saturated cyclicamine; m is an integer selected from 0, 1, 2 and 3; n is 0; R¹, R², R⁴and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different,and independently are hydrogen or C₁₋₅alkyl; Ar is phenyl or pyridylwhich phenyl or pyridyl is substituted with two or three substituents,which are the same or different, selected from the group consisting ofhalogen, C₁₋₃alkyl, C₁₋₃alkoxy, trifluoromethyl, trifluoromethoxy and—N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same or different, andindependently are hydrogen or C₁₋₃alkyl). More preferable are compoundsrepresented by the formula [III] in which wherein Y is N; the cyclicamino group is a 6-membered saturated cyclic amine; m is 0 or 1; n is 0;R¹, R², R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same ordifferent, and independently are hydrogen or methyl; Ar is phenyl whichphenyl is substituted with two or three substituents, which are the sameor different, selected from the group consisting of chloro, bromo,C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxyand dimethylamino.

Other preferable are compounds represented by the formula [III] in whichY is CR¹⁰. More preferable are compounds represented by the formula[III] in which Y is CR¹⁰; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R¹⁰ ishydrogen or halogen. More preferable are compounds represented by theformula [III] in which Y is CR¹⁰; the cyclic amino group is a 4- to7-membered saturated cyclic amine; m is an integer selected from 0, 1, 2and 3; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸are the same or different, and independently are hydrogen or C₁₋₅alkyl;R¹⁰ is hydrogen or halogen; Ar is phenyl or pyridyl which phenyl orpyridyl is substituted with two or three substituents, which are thesame or different, selected from the group consisting of halogen,C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxyand —N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same or different, andindependently are hydrogen or C₁₋₃alkyl. More preferable are compoundsrepresented by the formula [III] in which Y is CR¹⁰; the cyclic aminogroup is a 6-membered saturated cyclic amine; m is 0 or 1; n is 0; R¹,R², R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same ordifferent, and independently are hydrogen or methyl; R¹⁰ is hydrogen; Aris phenyl which phenyl is substituted with two or three substituents,which are the same or different, selected from the group consisting ofchloro, bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and dimethylamino.

Other preferable are compounds represented by the following formula [V]:

(wherein the cyclic amino group is represented by the following formula[VI]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OH, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;

Y is N or CR¹⁰;

R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

R² is hydrogen or C₁₋₅alkyl;

R³ is hydrogen, cyano, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

m is an integer selected from 0, 1, 2, 3, 4 and 5;

n is 0 or 1;

with the proviso that when n is 0, m is an integer selected from 1, 2,3, 4 and 5;

R⁴ is hydrogen, hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl orC₁₋₅alkyl;

R⁵ is hydrogen or C₁₋₅alkyl;

R⁶ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy or —N(R¹¹)R¹²;

R⁷ and R⁸ are the same or different, and independently are hydrogen,halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy,C₁₋₅alkoxy, C₃₋₈cycloalkyloxy, —N(R^(11a))R^(12a), —CO₂R¹³; cyano,nitro, C₁₋₅alkylthio, trifluoromethyl or trifluoromethoxy; or R⁷ and R⁸are taken together to form —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—;

R¹⁰ is hydrogen, C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹⁻,

Ar is aryl or heteroaryl which aryl or heteroaryl is unsubstituted orsubstituted with 1 or more substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio,C₁₋₅alkylsulfinyl, C₁₋₅alkylsulfonyl, cyano, nitro, hydroxy,—CO₂R^(19a), —C(═O)R^(19a), —CONR^(11b)R^(12b), —OC(═O)R^(19a),—NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹; the proviso that when Y is N, and the cyclic amino group is5-membered ring, then Ar is aryl or heteroaryl which aryl or heteroarylis substituted with at least one of substituents which are selected fromhalogen and trifluoromethyl;

R¹¹ and R¹² are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11a) and R^(12a) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11b) and R^(12b) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R¹³ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,C₁₋₅alkoxy-C₁₋₅alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl;

R¹⁹ is hydrogen or C₁₋₅alkyl;

R^(19a) is hydrogen or C₁₋₅alkyl;

r is 1 or 2;

R²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₅alkyl). More preferable are compounds represented by the formula [V]in which Y is N. More preferable are compounds represented by theformula [V] in which Y is N; m is an integer selected from 1, 2, 3, 4and 5; n is 0; R¹, R², R⁴ and R⁵ are hydrogen. More preferable arecompounds represented by the formula [V] in which Y is N; the cyclicamino group is a 4- to 7-membered saturated cyclic amine; m is aninteger selected from 1, 2 and 3; n is 0; R¹, R², R⁴ and R⁵ arehydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or C₁₋₅alkyl; Ar is phenyl or pyridyl whichphenyl or pyridyl is substituted with two or three substituents, whichare the same or different, selected from the group consisting ofhalogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same ordifferent, and independently are hydrogen or C₁₋₃alkyl); with theproviso that when the cyclic amino group is 5-membered ring, Ar isphenyl or pyridyl which phenyl or pyridyl is substituted with at leastone of substituents which are selected from halogen and trifluoromethyl.More preferable are compounds represented by the formula [V] in which Yis N; the cyclic amino group is a 6-membered saturated cyclic amine; mis an integer selected from 1, 2 and 3; n is 0; R¹, R², R⁴ and R⁵ arehydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or methyl; Ar is phenyl which phenyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of chloro, bromo,C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxyand dimethylamino.

Other preferable are compounds represented by the formula [V] in which Yis N; m is 1; n is 0; R¹ is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ andR⁵ are hydrogen. More preferable are compounds represented by theformula [V] in which Y is N; m is 1; n is 0; the cyclic amino group is a4- to 7-membered saturated cyclic amine; R¹ is C₁₋₅alkyl orhydroxy-C₁₋₅alkyl; R², R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸are the same or different, and independently are hydrogen or C₁₋₅alkyl;Ar is phenyl or pyridyl which phenyl or pyridyl is substituted with twoor three substituents, which are the same or different, selected fromthe group consisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl).More preferable are compounds represented by the formula [V] in which Yis N; m is 1; n is 0; the cyclic amino group is a 6-membered saturatedcyclic amine; R¹ is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ and R⁵ arehydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or methyl; Ar is phenyl which phenyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of chloro, bromo,C₁₋₃alkyl, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxy anddimethylamino.

Other preferable are compounds represented by the formula [V] in which Yis N; m is an integer selected from 1, 2, 3, 4 and 5; n is 0; R¹, R² andR⁵ are hydrogen; R⁴ is cyano, wherein a group represented by—(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substituted on the same carbonatom of the cyclic amine. More preferable are compounds represented bythe formula [V] in which Y is N; the cyclic amino group is a 4- to7-membered saturated cyclic amine; m is an integer selected from 1, 2and 3; n is 0; R¹, R² and R⁵ are hydrogen; R⁴ is cyano; R⁶ is methyl; R⁷and R⁸ are the same or different, and independently are hydrogen orC₁₋₅alkyl; Ar is phenyl or pyridyl which phenyl or pyridyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₃alkyl,C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxy and—N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same or different, andindependently are hydrogen or C₁₋₃alkyl), wherein a group represented by—(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substituted on the same carbonatom of the cyclic amine. More preferable are compounds represented bythe formula [V] in which Y is N; the cyclic amino group is a 6-memberedsaturated cyclic amine; m is an integer selected from 1, 2 and 3; n is0; R¹, R² and R⁵ are hydrogen; R⁴ is cyano; R⁶ is methyl; R⁷ and R⁸ arethe same or different, and independently are hydrogen or methyl; Ar isphenyl which phenyl is substituted with two or three substituents, whichare the same or different, selected from the group consisting of chloro,bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and dimethylamino, wherein a group represented by—(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substituted on the same carbonatom of the cyclic amine.

Other preferable are compounds represented by the formula [V] in whichwherein Y is CR¹⁰. More preferable are compounds represented by theformula [V] in which Y is CR¹⁰; m is an integer selected from 1, 2, 3, 4and 5; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R¹⁰ is hydrogen orhalogen. More preferable are compounds represented by the formula [V] inwhich Y is CR¹⁰; the cyclic amino group is a 4- to 7-membered saturatedcyclic amine; m is an integer selected from 1, 2 and 3; n is 0; R¹, R²,R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same ordifferent, and independently are hydrogen or C₁₋₅alkyl; R¹⁰ is hydrogenor halogen; Ar is phenyl or pyridyl which phenyl or pyridyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₃alkyl,C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxy and—N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same or different, andindependently are hydrogen or C₁₋₃alkyl). More preferable are compoundsrepresented by the formula [V] in which Y is CR¹⁰; the cyclic aminogroup is a 6-membered saturated cyclic amine; m is an integer selectedfrom 1, 2 and 3; n is 0; independently are hydrogen or methyl; R¹⁰ ishydrogen; Ar is phenyl which phenyl is substituted with two or threesubstituents, which are the same or different, selected from the groupconsisting of chloro, bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and dimethylamino.

Other preferable are compounds represented by the formula [V] in which Yis CR¹⁰; m is 1; n is 0; R¹ is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴and R⁵ are hydrogen; R¹⁰ is hydrogen or halogen. More preferable arecompounds represented by the formula [V] in which Y is CR¹⁰; m is 1; nis 0; the cyclic amino group is a 4- to 7-membered saturated cyclicamine; R¹ is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ and R⁵ are hydrogen;R⁶ is methyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen; Ar is phenyl orpyridyl which phenyl or pyridyl is substituted with two or threesubstituents, which are the same or different, selected from the groupconsisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl).More preferable are compounds represented by the formula [V] in which Yis CR¹⁰; m is 1; n is 0; the cyclic amino group is a 6-memberedsaturated cyclic amine; R¹ is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ andR⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or methyl; R¹⁰ is hydrogen; Ar is phenylwhich phenyl is substituted with two or three substituents, which arethe same or different, selected from the group consisting of chloro,bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and dimethylamino.

Other preferable are compounds represented by the formula [V] in which Yis CR¹⁰; m is an integer selected from 1, 2, 3, 4 and 5; n is 0; R¹, R²and R⁵ are hydrogen; R⁴ is cyano; R¹⁰ is hydrogen or halogen, wherein agroup represented by —(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substitutedon the same carbon atom of the cyclic amine. More preferable arecompounds represented by the formula [V] in which Y is CR¹⁰; the cyclicamino group is a 4- to 7-membered saturated cyclic amine; m is aninteger selected from 1, 2 and 3; n is 0; R¹, R² and R⁵ are hydrogen; R⁴is cyano; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen; Aris phenyl or pyridyl which phenyl or pyridyl is substituted with two orthree substituents, which are the same or different, selected from thegroup consisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl),wherein a group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ aresubstituted on the same carbon atom of the cyclic amine. More preferableare compounds represented by the formula [V] in which Y is CR¹⁰; thecyclic amino group is a 6-membered saturated cyclic amine; m is aninteger selected from 1, 2 and 3; n is 0; R¹, R² and R⁵ are hydrogen; R⁴is cyano; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or methyl; R¹⁰ is hydrogen; Ar is phenylwhich phenyl is substituted with two or three substituents, which arethe same or different, selected from the group consisting of chloro,bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and dimethylamino, wherein a group represented by—(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substituted on the same carbonatom of the cyclic amine.

Other preferable are compounds represented by the following formula[VII]:

(wherein the cyclic amino group is represented by the following formula[VIII]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OR⁹, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;

Y is N or CR¹⁰;

R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

R² is hydrogen or C₁₋₅alkyl;

R³ is hydrogen, cyano, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl;

m is an integer selected from 0, 1, 2, 3, 4 and 5;

n is 0 or 1;

with the proviso that when n is 0, m is an integer selected from 1, 2,3, 4 and 5;

R⁴ is hydrogen, hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl orC₁₋₅alkyl;

R⁵ is hydrogen or C₁₋₅alkyl;

R⁶ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy or —N(R¹¹)R¹²;

R⁷ and R⁸ are the same or different, and independently are hydrogen,halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy,C₁₋₅alkoxy, C₃₋₈cycloalkyloxy, —N(R^(11a))R^(12a), —CO₂R¹³, cyano,nitro, C₁₋₅alkylthio, trifluoromethyl or trifluoromethoxy; or R⁷ and R⁸are taken together to form —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—;

R⁹ is C₁₋₂₄acyl, C₁₋₁₀alkoxycarbonyl, aryl-C₁₋₅alkyloxycarbonyl,—CO—O—CHR¹⁴—O—CO—R¹⁵, —P(═O)(OR^(14a))OR^(15a),—CO—(CH₂)_(p)—(CHR¹⁶)_(q)—NR¹⁷R¹⁸, arylcarbonyl or heteroarylcarbonyl,wherein each said acyl, aryl and heteroaryl is unsubstituted orsubstituted with C₁₋₅alkoxy, and C₁₋₂₄acyl optionally includes one tosix double bonds;

R¹⁰ is hydrogen, C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹;

Ar is aryl or heteroaryl which aryl or heteroaryl is unsubstituted orsubstituted with 1 or more substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio,C₁₋₅alkylsulfinyl, C₁₋₅alkylsulfonyl, cyano, nitro, hydroxy,—CO₂R^(19a), —C(═O)R^(19a), —CONR^(11b)R^(12b)), —OC(═O)R^(19a),—NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹;

R¹¹ and R¹² are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11a) and R^(12a) are the same or different, and independently arehydrogen, C₁₋₅ alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl;

R^(11b) and R^(12b) are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅ alkyl;

R¹³ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,C₁₋₅alkoxy-C₁₋₅alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl;

R¹⁴ and R¹⁵ are the same or different, and independently are hydrogen,C₁₋₅alkyl or aryl-C₁₋₅alkyl;

R^(14a) and R^(15a) are the same or different, and independently arehydrogen, C₁₋₅ alkyl or aryl-C₁₋₅alkyl;

R¹⁶ is hydrogen, C₁₋₅alkyl, aryl, heteroaryl, aryl-C₁₋₅ alkyl,heteroaryl-C₁₋₅alkyl, hydroxy-C₁₋₅alkyl, hydroxycarbonyl-C₁₋₅alkyl,hydroxyphenyl-C₁₋₅ alkyl, C₁₋₅alkoxy-C₁₋₅alkyl, amino-C₁₋₅alkyl,guanidino-C₁₋₅alkyl, mercapto-C₁₋₅ alkyl, C₁₋₅ alkylthio-C₁₋₅ alkyl oraminocarbonyl-C₁₋₅alkyl;

R¹⁷ and R¹⁸ are the same or different, and independently are hydrogen,C₁₋₅ alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅ alkyl, C₁₋₁₀acyl,C₁₋₁₀alkoxycarbonyl and aryl-C₁₋₅alkyloxycarbonyl,

or R¹⁶ and R¹⁷ are taken together to form —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂—or —CH₂CH₂CH₂CH₂—;

p is an integer selected from 0, 1, 2, 3, 4 and 5;

q is 0 or 1;

R¹⁹ is hydrogen or C₁₋₅alkyl;

R^(19a) is hydrogen or C₁₋₅alkyl;

r is 1 or 2;

R²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₅alkyl). More preferable are compounds represented by the formula[VII] in which Y is N. More preferable are compounds represented by theformula [VII] in which Y is N; m is an integer selected from 1, 2, 3, 4and 5; n is 0; R¹, R², R⁴ and R⁵ are hydrogen. More preferable arecompounds represented by the formula [VII] in which the cyclic aminogroup is a 4- to 7-membered saturated cyclic amine; m is an integerselected from 1, 2, 3, 4 and 5; n is 0; Y is N; R¹, R², R⁴ an R⁵ and arehydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or C₁₋₅alkyl; Ar is phenyl or pyridyl whichphenyl or pyridyl is substituted with two or three substituents, whichare the same or different, selected from the group consisting ofhalogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same ordifferent, and independently are hydrogen or C₁₋₃alkyl). More preferableare compounds represented by the formula [VII] in which the cyclic aminogroup is a 6-membered saturated cyclic amine; m is an integer selectedfrom 1, 2 and 3; n is 0; Y is N; R², R⁴ and R⁵ are hydrogen; R⁶ ismethyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or methyl; Ar is phenyl which phenyl is substituted with two orthree substituents, which are the same or different, selected from thegroup consisting of chloro, bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and dimethylamino.

Other preferable are compounds represented by the formula [VII] in whichY is CR¹⁰. More preferable are compounds represented by the formula[VII] in which Y is CR¹⁰; m is an integer selected from 1, 2, 3, 4 and5; n is 0; R¹, R², R⁴ and R⁵ are hydrogen. More preferable are compoundsrepresented by the formula [VII] in which Y is CR¹⁰; the cyclic aminogroup is a 4- to 7-membered saturated cyclic amine; m is an integerselected from 1, 2 and 3; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R⁶ ismethyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen; Ar is phenyl orpyridyl which phenyl or pyridyl is substituted with two or threesubstituents, which are the same or different, selected from the groupconsisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl).More preferable are compounds represented by the formula [VII] in whichY is CR¹⁰; the cyclic amino group is a 6-membered saturated cyclicamine; m is an integer selected from 1, 2 and 3; n is 0; R¹, R², R⁴ andR⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or methyl; R¹⁰ is hydrogen; Ar is phenylwhich phenyl is substituted with two or three substituents, which arethe same or different, selected from the group consisting of chloro,bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and dimethylamino.

Especially preferable compounds of the present invention are:

-   2-{1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-ethanol,

-   2-{1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-ethanol,

-   3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-propan-1-ol,

-   3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-propan-1-ol,

-   {1-[7-(2,4-dibromo-6-methoxy-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-methanol,

-   {1-[7-(2,4-dibromo-6-methylsulfanyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-methanol,

-   {1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-methanol,

-   2-{1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-ethanol,

-   2-{1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-ethanol,

-   {1-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2-methyl-9-(2,4,6-trimethyl-phenyl)-9H-1,3,9-triaza-fluoren-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2,5,6-trimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dichloro-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dichloro-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2,6-dibromo-4-isopropyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2,6-dibromo-4-isopropyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   2-{1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[2,5,6-trimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   3-{1-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[7-(4-bromo-2,6-dichloro-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[7-(4-bromo-2,6-dichloro-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   {1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3-methyl-piperidin-3-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3-methyl-piperidin-3-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3-methyl-piperidin-3-yl}-methanol,

-   1-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethane-1,2-diol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidin-2-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidin-2-yl}-methanol,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-ethanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]azepan-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-azepan-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-2-yl}-acetonitrile,

-   1-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(2,4-dibromo-6-methylsulfanyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(4-isopropyl-2-methylsulfanyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(4-isopropyl-2-methylsulfanyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(2-bromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-3-carbonitrile,

-   {1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-acetonitrile,

-   3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-propionitrile,

-   3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-3-yl}-propionitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-4-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-4-carbonitrile,

-   {1-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(2,6-dibromo-4-trifluoromethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-diethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[2,5,6-trimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[2,5-dimethyl-7-(2,4,6-tribromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dichloro-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dichloro-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(2,6-dibromo-4-isopropyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(2,6-dibromo-4-isopropyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-methoxy-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-methoxy-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   8-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-8-aza-bicyclo[3.2.1]octane-3-carbonitrile,

-   8-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-8-aza-bicyclo[3.2.1]octane-3-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidine-3-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidine-3-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-azepane-4-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-azepane-4-carbonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3-hydroxymethyl-piperidine-3-carbonitrile,

-   {1-[7-(4-isopropyl-2-methylsulfanyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2-bromo-4-isopropyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2,4-dibromo-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2,6-dibromo-4-chloro-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   2-{1-[7-(2,6-dibromo-4-chloro-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   1-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propane-1,3-diol,

-   {1-[7-(2,6-dibromo-4-chloro-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-acetonitrile,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrrolidin-3-yl}-acetonitrile,

-   {1-[2,5-dimethyl-7-(2,4,6-trichloro-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[7-(2,6-dichloro-4-trifluoromethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-methanol,

-   3-{1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidine-4-carbonitrile,

-   {1-[7-(2,6-Dichloro-4-trifluoromethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-acetonitrile,

-   1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-azetidine-3-carbonitrile,

-   1-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   1-{1-[7-(4-isopropyl-2-methylsulfanyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   1-{1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   1-{1-[7-(4-chloro-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3-methyl-piperidin-4-yl}-methanol,

-   {1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3-methyl-piperidin-4-yl}-methanol,

-   {8-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-8-aza-bicyclo[3.2.1]oct-3-yl}-methanol,

-   {8-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-8-aza-bicyclo[3.2.1]oct-3-yl}-methanol,

-   {8-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-8-aza-bicyclo[3.2.1]oct-3-yl}-acetonitrile,

-   {8-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-8-aza-bicyclo[3.2.1]oct-3-yl}-acetonitrile,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-malononitrile,

-   2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-malononitrile,

-   2-{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-ethanol,

-   2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-ethanol,

-   {1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   2-{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   3-{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-3-carbonitrile,

-   1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-3-carbonitrile,

-   {1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-acetonitrile,

-   1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   {1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-ethanol,

-   {1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   3-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-3-carbonitrile,

-   1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   {1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[1-(2-bromo-4-trifluoromethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   {1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,

-   2-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-4-yl}-ethanol,

-   2-{1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   2-{1-[5-bromo-1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,

-   3-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[3,6-dimethyl-1-(2,4,6-tri    chloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   3-{1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,

-   1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethane-1,2-diol,

-   1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethane-1,2-diol,

-   1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propane-1,3-diol,

-   1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propane-1,3-diol,

-   1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(4-isopropyl-2-methyl    sulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[1-(2-bromo-4-trifluoromethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,

-   {1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[1-(2-bromo-4-trifluoromethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   {1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,

-   carbonic acid    1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl    ester ethyl ester,

-   pyridine-2-carboxylic acid    1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl    ester,

-   methoxy-acetic acid    1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl    ester,

-   methoxy-acetic acid    1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-ylmethyl    ester,

-   carbonic acid benzyl ester    1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl    ester,

-   decanoic acid    1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl    ester,

-   3-diethylamino-propionic acid    1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl    ester,

-   and phosphoric acid    mono-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl}ester.

-   The compound represented by the formula [I] can be produced, for    example, by the process shown in the following reaction scheme 1-4    [in the following reaction scheme, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸,    m, n, X, Y and Ar are as defined above; LG is chloro, bromo, iodo,    methanesulfonyloxy, benzenesulfonyloxy, 4-toluenesulfonyloxy or    trifluoromethanesulfonyloxy group; Z¹ and Z² are the same or    different, and independently are chloride or bromide; R^(a) and    R^(b) are the same or different, and independently are hydrogen,    C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; and X^(a) is    —(CHR³)_(n)—OH, —(CHR³)_(n)—CN or —CO₂—(C₁₋₅alkyl)].

Step 1:

Compound (3), a compound of the present invention, can be obtained byreacting Compound (1) with Compound (2) in an inert solvent in thepresence or absence of a base. Herein, the base includes, for example,amines such as triethylamine, N,N-diisopropylethylamine, pyridine andthe like; inorganic bases such as sodium carbonate, potassium carbonate,sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide,potassium hydroxide, barium hydroxide, sodium hydride and the like;metal alcoholates such as sodium methoxide, sodium ethoxide, potassiumtert-butoxide and the like; metal amides such as sodium amide, lithiumdiisopropylamide and the like; and Grignard reagents such asmethylmagnesium bromide and the like. The inert solvent includes, forexample, alcohols such as methanol, ethanol, isopropyl alcohol, ethyleneglycol and the like; ethers such as diethyl ether, tetrahydrofuran,1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such asbenzene, toluene, xylene and the like; amides such asN,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide andthe like; acetonitrile; dimethyl sulfoxide; pyridine; water; andmixtures of solvents selected from these inert solvents.

The compound of the present invention can be converted to a salt in aninert solvent with an inorganic acid such as sulfuric acid, hydrochloricacid, hydrobromic acid, phosphoric acid, nitric acid or the like, withan organic acid such as acetic acid, oxalic acid, lactic acid, tartaricacid, fumaric acid, maleic acid, citric acid, benzenesulfonic acid,methanesulfonic acid, p-toluenesulfonic acid, benzoic acid,camphorsulfonic acid, ethanesulfonic acid, glucoheptonic acid, gluconicacid, glutamic acid, glycolic acid, malic acid, malonic acid, mandelicacid, galactaric acid, naphthalene-2-sulfonic acid or the like, with aninorganic base such as lithium hydroxide, sodium hydroxide, potassiumhydroxide, calcium hydroxide, magnesium hydroxide, zinc hydroxide,aluminum hydroxide or the like or with an organic base such as ammonia,arginine, lysine, piperazine, choline, diethylamine,4-phenylcyclohexylamine, 2-aminoethanol, benzathine or the like. Theinert solvent includes, for example, alcohols such as methanol, ethanol,isopropyl alcohol, ethylene glycol and the like; ethers such as diethylether, diisopropyl ether, tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane and the like; hydrocarbons such as benzene, tolueneand the like; esters such as ethyl acetate, ethyl formate and the like;ketones such as acetone, methylethylketone and the like; amides such asN,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide andthe like; acetonitrile; dichloromethane; chloroform; dimethyl sulfoxide;pyridine; water; and mixtures of solvents selected from these inertsolvents.

Step 2:

Compound (4) can be converted to Compound (6) by reacting Compound (4)with Compound (5) in an inert solvent in the presence or absence of abase. Herein, the base includes, for example, amines such astriethylamine, N,N-diisopropylethylamine, pyridine and the like;inorganic bases such as sodium carbonate, potassium carbonate, sodiumhydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide,potassium hydroxide, barium hydroxide, sodium hydride and the like;metal alcoholates such as sodium methoxide, sodium ethoxide, potassiumtert-butoxide and the like; metal amides such as sodium amide, lithiumdiisopropylamide and the like; and Grignard reagents such as methylmagnesium bromide and the like. The inert solvent includes, for example,alcohols such as methanol, ethanol, isopropyl alcohol, ethylene glycoland the like; ethers such as diethyl ether, tetrahydrofuran,1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such asbenzene, toluene, xylene and the like; amides such asN,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide andthe like; acetonitrile; dimethyl sulfoxide; pyridine; water; andmixtures of solvents selected from these inert solvents.

Step 3:

Compound (6) can be converted to Compound (7) by reacting Compound (6)with malononitrile in an inert solvent in the presence or absence of abase. Herein, the base includes, for example, amines such astriethylamine, N,N-diisopropylethylamine, pyridine and the like;inorganic bases such as sodium carbonate, potassium carbonate, sodiumhydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide,potassium hydroxide, barium hydroxide, sodium hydride, potassium hydrideand the like; metal alcoholates such as sodium methoxide, sodiumethoxide, potassium tert-butoxide and the like; metal amides such assodium amide, lithium diisopropylamide, lithium hexamethyldisilazanide,sodium hexamethyldisilazanide, potassium hexamethyldisilazanide and thelike; alkyl lithiums such as methyl lithium, n-butyl lithium, sec-butyllithium, tert-butyl lithium and phenyl lithium; and Grignard reagentssuch as methyl magnesium bromide and the like. The inert solventincludes, for example, alcohols such as methanol, ethanol, isopropylalcohol, ethylene glycol and the like; ethers such as diethyl ether,tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like;hydrocarbons such as benzene, toluene and the like; amides such asN,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide andthe like; acetonitrile; dimethyl sulfoxide; pyridine; water; andmixtures of solvents selected from these inert solvents.

Step 4:

Compound (7) can be converted to Compound (8) by acylation of aminogroup in Compound (7) and followed by formation of pyrimidine ring. Theacylation and the formation of pyrimidine ring may occur continuously inone pot. The acylation can be achieved by reacting Compound (7) with anacylating reagent in an inert solvent in the presence or absence of abase or an acid. The following formation of pyrimidine ring can becarried out by heating the acylated compound in an inert solvent in thepresence or absence of an acid. Herein, the acylating reagent includes,for example, halogenated acyls such as acetyl chloride, acetyl bromide,propionyl chloride, propionyl bromide, butyryl chloride,cyclopropanecarbonyl chloride, benzoyl chloride and the like; acidanhydride such as acetic anhydride, propionic anhydride, butyricanhydride, benzoic anhydride and the like. The base includes, forexample, amines such as triethylamine, N,N-diisopropylethylamine,pyridine and the like; inorganic bases such as sodium carbonate,potassium carbonate, sodium hydrogencarbonate, potassiumhydrogencarbonate, sodium hydroxide, potassium hydroxide, bariumhydroxide, sodium hydride, potassium hydride and the like; metalalcoholates such as sodium methoxide, sodium ethoxide, potassiumtert-butoxide and the like; metal amides such as sodium amide, lithiumdiisopropylamide, lithium hexamethyldisilazanide, sodiumhexamethyldisilazanide, potassium hexamethyldisilazanide and the like;and Grignard reagents such as methyl magnesium bromide and the like. Theacid includes, for example, organic acids such as formic acid, aceticacid, trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid,p-toluenesulfonic acid, benzoic acid, trifluoromethanesulfonic acid andthe like; inorganic acids such as sulfuric acid, hydrochloric acid,hydrobromic acid, phosphoric acid, polyphosphoric acid, nitric acid orthe like. The inert solvent includes, for example, alcohols such asmethanol, ethanol, isopropyl alcohol, ethylene glycol and the like;ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane and the like; hydrocarbons such as benzene, toluene,xylene and the like; amides such as N,N-dimethylformamide,N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile;dimethyl sulfoxide; pyridine; acetic acid; water; and mixtures ofsolvents selected from these inert solvents.

Step 5

Compound (8) can be converted to Compound (9) by reacting (8) with ahalogenating reagent or a sulfonating reagent in the presence or absenceof a base in an inert solvent or without any solvent. Herein, thehalogenating reagent includes, for example, phosphoryl chloride,phosphoryl bromide, phosphorous pentachloride, phosphorous trichloride,phosphorous pentabromide, phosphorous tribromide, thionyl chloride,thionyl bromide, oxalyl chloride, oxalyl bromide and the like. Thesulfonating reagent includes, for example, p-toluenesulfonyl chloride,methanesulfonyl chloride, p-toluenesulfonic anhydride, methansulfonicanhydride, trifluoromethanesulfonic anhydride,N-phenylbis(trifluoromethanesulfonimide) and the like. The baseincludes, for example, amines such as triethylamine,N,N-diisopropylethylamine, pyridine, N,N-dimethylaniline,N,N-diethylaniline and the like; inorganic bases such as sodiumcarbonate, potassium carbonate, sodium hydrogencarbonate, potassiumhydrogencarbonate, sodium hydroxide, potassium hydroxide, bariumhydroxide, sodium hydride and the like; metal alcoholates such as sodiummethoxide, sodium ethoxide, potassium tert-butoxide and the like; metalamides such as sodium amid; lithium diisopropylamide and the like; andGrignard reagents such as methyl magnesium bromide and the like. Theinert solvent includes, for example, alcohols such as methanol, ethanol,isopropyl alcohol, ethylene glycol and the like; ethers such as diethylether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like;hydrocarbons such as benzene, toluene and the like; amides such asN,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide andthe like; dichloromethane; chloroform; acetonitrile; dimethyl sulfoxide;pyridine; water; and mixtures of solvents selected from these inertsolvents.

Step 6

Compound (9) can be converted to Compound (11) by reacting Compound (9)with Compound (10) in the same method as step 1.

Step 7

Compound (11) can be converted to Compound (12) by reduction of Compound(11) with a conventional reducing agent in an inert solvent. Or ifnecessary, treatment with an acid in the presence or absence of inertsolvent after the reduction can provide Compound (12). When X^(a) is—CO₂—(C₁₋₅alkyl), the ester group can be converted to a hydroxymethylgroup at the same time. Herein, the reducing agent includes, forexample, lithium borohydride, sodium borohydride, calcium borohydride,lithium triethylborohydride, lithium tri-sec-butylborohydride, potassiumtri-sec-butylborohydride, zinc borohydride, borane, lithiumtrimethoxyborohydride, lithium triacetoxyborohydride,tetramethylammonium borohydride, lithium aluminum hydride, sodiumaluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride,diisobutylaluminum hydride, trichlorosilane and the like. The reductioncan be also carried out by hydrogenation using a catalyst includingpalladium, platinum dioxide, Raney nickel or the like. The acidincludes, for example, organic acids such as acetic acid,trifluoroacetic acid, benzenesulfonic acid, methanesulfonic acid,p-toluenesulfonic acid, benzoic acid and the like; inorganic acids suchas sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoric acid,polyphosphoric acid, nitric acid or the like. The inert solventincludes, for example, alcohols such as methanol, ethanol, isopropylalcohol, ethylene glycol and the like; ethers such as diethyl ether,tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like;hydrocarbons such as benzene, toluene and the like; amides such asN,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide andthe like; acetonitrile; dimethyl sulfoxide; pyridine; water; andmixtures of solvents selected from these inert solvents.

Step 8

Compound (7) can be converted to Compound (13) by reacting Compound (7)with ketones such as acetone and the like; vinyl ethers such asisopropenyl methyl ether and the like in an inert solvent in thepresence or absence of an acid, and the following conversion fromCompound (13) to Compound (14) can be carried out in the presence ofbase in an inert solvent. Herein, the acid includes, for example,organic acids such as acetic acid, trifluoroacetic acid, benzenesulfonicacid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid and thelike. The base includes, for example, amines such as triethylamine,N,N-diisopropylethylamine, pyridine, 1,8-diazabicyclo[5.4.0]undec-7-eneand the like; inorganic bases such as sodium carbonate, potassiumcarbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, sodiumhydroxide, potassium hydroxide, barium hydroxide, sodium hydride and thelike; metal alcoholates such as sodium methoxide, sodium ethoxide,potassium tert-butoxide and the like; metal amides such as sodium amide,lithium diisopropylamide, lithium hexamethyldisilazanide, sodiumhexamethyldisilazanide, potassium hexamethyldisilazanide and the like;alkyl lithiums such as n-butyl lithium, sec-butyl lithium, tert-butyllithium, methyl lithium and the like; and Grignard reagents such asmethyl magnesium bromide and the like. The inert solvent includes, forexample, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane and the like; hydrocarbons such as benzene, tolueneand the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone,N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide;pyridine; and mixtures of solvents selected from these inert solvents.

Step 9

Compound (14) can be converted to Compound (15) in the same manner asstep 7.

Step 10

Compound (15) can be converted into Compound (16) via the correspondingdiazonium compound. The conversion to the diazonium compound can becarried out using, for example, sodium nitrite, potassium nitrite,butylnitrite, tert-butylnitrite, iso-butylnitrite or the like in thepresence or absence of an acid in an inert solvent. The acid includes,for example, inorganic acids such as sulfuric acid, hydrochloric acid,hydrobromic acid, nitric acid or the like. The inert solvent includes,for example, ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane and the like; hydrocarbons such as benzene, tolueneand the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone,N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide;pyridine; water; and mixtures of solvents selected from these inertsolvents.

Step 11

Compound (16) can be converted to Compound (17) in the same manner asstep 5.

Step 12

When LG is chloride, bromide or iodide, Compound (17) can be obtainedfrom Compound (15) directly by formation of the diazonium compound inthe presence of one or more metal salts in an inert solvent. Theformation of the diazonium compound can be carried out in the samemanner as step 10. The metal salts include, for example, potassiumiodide, potassium bromide, sodium iodide, sodium bromide, sodiumchloride, copper (I) chloride, copper (II) chloride, copper (I) bromide,copper (II) bromide, copper (I) iodide and the like. The inert solventincludes, for example, ethers such as diethyl ether, tetrahydrofuran,1,4-dioxane, 1,2-dimethoxyethane and the like; hydrocarbons such asbenzene, toluene and the like; amides such as N,N-dimethylformamide,N-methylpyrrolidone, N,N-dimethylacetamide and the like; acetonitrile;dimethyl sulfoxide; pyridine; water; and mixtures of solvents selectedfrom these inert solvents.

Step 13

Compound (17) can be converted to Compound (18) in the same manner asstep 1.

Step 14

When X^(a) is —CO₂—(C₁₋₅alkyl), the ester group can be converted tohydroxymethyl group in the same manner as step 7.

Step 15

Compound (20) can be converted to Compound (21) by a coupling ofCompound (20) with the corresponding carboxylic acid using aconventional coupling reagent in the presence or absence of an additiveor a base in an inert solvent or a coupling of Compound (20) with thecorresponding acyl halide in the presence or absence of a base in aninert solvent. When R⁹ has protective groups of an amino group, ahydroxy group, a mercapto group, a carboxy group, a guanidine group or aphosphoric acid group, those protective groups can be removed byconventional methods for deprotection (ref. Theodora W. Greene and PeterG. M. Wuts “Protective Groups in Organic Synthesis”; Wiley-Interscience)after the above coupling. Herein, the coupling reagent includes, forexample, N,N′-dicyclohexylcarbodiimide (DCC),1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC),1,1′-carbonyldiimidazole (CDI), diphenylphosphorylazide (DPPA), diethylcyanophosphate and the like. The additive includes, for example,1-hydroxybenzotriazole (HOBt), N-hydroxysuccinimide,4-dimethylaminopyridine and the like. The base includes amines such astriethylamine, N,N-diisopropylethylamine, pyridine,1,8-diazabicyclo[5.4.0]undec-7-ene and the like; inorganic bases such assodium carbonate, potassium carbonate, sodium hydrogencarbonate,potassium hydrogencarbonate, sodium hydroxide, potassium hydroxide,barium hydroxide, sodium hydride and the like; metal alcoholates such assodium methoxide, sodium ethoxide, potassium tert-butoxide and the like;metal amides such as sodium amide, lithium diisopropylamide, lithiumhexamethyldisilazanide, sodium hexamethyldisilazanide, potassiumhexamethyldisilazanide and the like; alkyl lithiums such as n-butyllithium, sec-butyl lithium, tert-butyl lithium, methyl lithium and thelike; and Grignard reagents such as methyl magnesium bromide and thelike. The inert solvent includes, for example, alcohols such asmethanol, ethanol, isopropyl alcohol, ethylene glycol and the like;ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane,1,2-dimethoxyethane and the like; hydrocarbons such as benzene, tolueneand the like; amides such as N,N-dimethylformamide, N-methylpyrrolidone,N,N-dimethylacetamide and the like; acetonitrile; dimethyl sulfoxide;pyridine; chloroform; dichloromethane; water; and mixtures of solventsselected from these inert solvents.

The compound of the present invention is useful as a therapeutic orprophylactic agent for diseases in which CRF is considered to beinvolved. For this purpose, the compound of the present invention can beformulated into tablets, pills, capsules, granules, powders, solutions,emulsions, suspensions, injections and the like by a conventionalpreparation technique by adding conventional fillers, binders,disintegrators, pH-adjusting agents, solvents, etc.

The compound of the present invention can be administered to an adultpatient in a dose of 0.1 to 500 mg per day in one portion or severalportions orally or parenterally. The dose can be properly increased ordecreased depending on the kind of a disease and the age, body weightand symptom of a patient.

EMBODIMENTS OF THE INVENTION

The present invention is concretely explained with reference to thefollowing examples and test example, but is not limited thereto.

Example 1 Synthesis of2-{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}ethanolhydrochloride (compound 1-074)

(1) A mixture of7-(4-bromo-2,6-dimethylphenyl)-4-chloro-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidine(6.0 g), 4-(2-hydroxyethyl)piperidine (3.2 g), N,N-diisopropylethylamine(3.2 g) in ethanol (15 mL) was heated at reflux for 5.5 hours. Thereaction mixture was cooled to room temperature, poured into a saturatedaqueous sodium hydrogencarbonate, and then extracted with ethyl acetatethree times. The organic layer was washed with brine, dried overanhydrous sodium sulfate and filtered. The filtrate was concentratedunder reduced pressure and purified by a silica gel columnchromatography (silica gel: Wako Gel (C200), eluent: hexane/ethylacetate=2:1) to obtain2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanolas a white solid (6.41 g).

(2) To a suspension of2-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-ethanol(6.41 g) in ethanol (51 mL) was added 4 M HCl in ethyl acetate (4.2 mL)under ice-cooling. After removing the solvent, ethyl acetate (26 mL) wasadded to the residue. The mixture was stirred overnight to afford awhite crystal. The crystal was collected by filtration to give the titlecompound (6.1 g).

m.p. 187-189° C.

Table 1 and Table 2 list the compound obtained in Example 1 andcompounds obtained by the similar procedure as in Example 1.

Example 2 Synthesis of optically active1-[7-(2-bromo-4-trifluoromethylphenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine-4-yl]piperidine-3-carbonitrile(compound 1-134, 1-135, 1-136 and 1-137)

A mixture of7-(2-bromo-4-trifluoromethylphenyl)-4-chloro-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine(400 mg), piperidine-3-carbonitrile (290 mg), N,N-diisopropylethylamine(309 mg) in ethanol (2 mL) was heated at reflux for 6 days. The reactionmixture was cooled to room temperature, and concentrated under reducedpressure. The residue was purified by a silica gel column chromatography(silica gel: Wako Gel (C200), eluent: hexane/ethyl acetate=5:1) toobtain two diastereoisomers (low polar diastereoisomer: 62 mg and highpolar diastereoisomer: 36 mg) of1-[7-(2-bromo-4-trifluoromethylphenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine-4-yl]piperidine-3-carbonitrile.

Low Polar Diastereoisomer:

Rf value 0.64 (developing solvent: hexane/ethyl acetate=1:1, TLC plateSilica gel 60 F₂₅₄ (Merck))

¹H NMR (300 MHz) δ 1.68-1.83 (1H, m), 1.85-2.07 (3H, m), 2.08 (3H, s),2.40 (3H, s), 2.51 (3H, s), 3.04-3.16 (1H, m), 3.26-3.62 (3H, m),3.81-3.95 (1H, m), 7.43 (1H, d, J=8.2 Hz), 7.74 (1H, d, J=8.2 Hz), 8.02(1H, s)

High Polar Diastereoisomer:

Rf value 0.56 (developing solvent: hexane/ethyl acetate=1:1, TLC plateSilica gel 60 F₂₅₄ (Merck))

¹H NMR (300 MHz) δ 1.65-1.83 (1H, m), 1.82-2.16 (6H, m), 2.40 (3H, s),2.51 (3H, s), 3.04-3.17 (1H, m), 3.28-3.63 (3H, m), 3.85-3.98 (1H, m),7.47 (1H, d, J=8.6 Hz), 7.74 (1H, d, J=8.6 Hz), 8.02 (1H, s)

The low polar diastereoisomer was optically resolved by high performanceliquid chromatography to give each enantiomer.

Compound 1-134:

¹H NMR (300 MHz) δ 1.68-1.83 (1H, m), 1.85-2.07 (3H, m), 2.08 (3H, s),2.40 (3H, s), 2.51 (3H, s), 3.04-3.16 (1H, m), 3.26-3.62 (3H, m),3.81-3.95 (1H, m), 7.43 (1H, d, J=8.2 Hz), 7.74 (1H, d, J=8.2 Hz), 8.02(1H, s)

HPLC retention time: 20.0 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 2.0 cm I.D.×25 cm, mobile phase: hexane−IPA=4:1, flowrate: 5.0 mL/min.)

Compound 1-135:

¹H NMR (300 MHz) δ 1.68-1.83 (1H, m), 1.85-2.07 (3H, m), 2.08 (3H, s),2.40 (3H, s), 2.51 (3H, s), 3.04-3.16 (1H, m), 3.26-3.62 (3H, m),3.81-3.95 (1H, m), 7.43 (1H, d, J=8.2 Hz), 7.74 (1H, d, J=8.2 Hz), 8.02(1H, s)

HPLC retention time: 23.0 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 2.0 cm I.D.×25 cm, mobile phase: hexane−IPA=4:1, flowrate: 5.0 mL/min.)

The high polar diastereoisomer was also optically resolved by highperformance liquid chromatography to give each enantiomer.

Compound 1-136:

¹H NMR (300 MHz) δ 1.65-1.83 (1H, m), 1.82-2.16 (6H, m), 2.40 (3H, s),2.51 (3H, s), 3.04-3.17 (1H, m), 3.28-3.63 (3H, m), 3.85-3.98 (1H, m),7.47 (1H, d, J=8.6 Hz), 7.74 (1H, d, J=8.6 Hz), 8.02 (1H, s)

HPLC retention time: 21.4 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 2.0 cm I.D.×25 cm, mobile phase: hexane−IPA=4:1, flowrate: 5.0 mL/min.)

Compound 1-137:

¹H NMR (300 MHz) δ 1.65-1.83 (1H, m), 1.82-2.16 (6H, m), 2.40 (3H, s),2.51 (3H, s), 3.04-3.17 (1H, m), 3.28-3.63 (3H, m), 3.85-3.98 (1H, m),7.47 (1H, d, J=8.6 Hz), 7.74 (1H, d, J=8.6 Hz), 8.02 (1H, s)

HPLC retention time: 32.8 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 2.0 cm I.D.×25 cm, mobile phase: hexane−IPA=4:1, flowrate: 5.0 mL/min.)

Table 1 lists the compounds obtained in Example 2.

Example 3 Synthesis of{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanolhydrochloride (1-054)

(1) To a solution of 4-bromo-2,6-dimethylaniline (100.0 g) intetrahydrofuran (400 mL) was added triethylamine (60.7 g) and2-bromopropionyl bromide (129.5 g) under ice-cooling. The mixture wasstirred at room temperature for 1 hour and cooled in an ice-coolingbath. To the reaction mixture was added a sodium hydrogencarbonateaqueous solution and the mixture was stirred at room temperature for 30minutes. The precipitate was collected by filtration, washed with waterand diethyl ether, and dried to give2-bromo-N-(4-bromo-2,6-dimethylphenyl)propionamide (151.2 g).

m.p. 187-189° C.

(2) To a suspension of NaH (17.2 g) in tetrahydrofuran (500 mL) wasadded a solution of malononitrile (28.4 g) in tetrahydrofuran (100 mL)under ice-cooling and the mixture was stirred at room temperature for 1hour. 2-Bromo-N-(4-bromo-2,6-dimethylphenyl)propionamide (120 g) wasadded and the mixture was heated at reflux for 1 hour. With ice-cooling,an ammonium chloride aqueous solution was added and extracted with ethylacetate. The organic layer was washed with brine, dried over anhydroussodium sulfate and filtered. The filtrate was concentrated under reducedpressure to give a solid. The solid was washed with a mixture ofdiisopropylether and ethyl acetate and filtered, dried to give2-amino-1-(4-bromo-2,6-dimethylphenyl)-4-methyl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitrile(110.1 g).

m.p. 175-177° C.

(3) To a suspension of2-amino-1-(4-bromo-2,6-dimethylphenyl)-4-methyl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitrile(100 g) in acetic acid (100 mL) was added acetic anhydride (38.3 g) andthe mixture was heated at reflux for 8 hours. After cooling to roomtemperature, the solvent was concentrated under reduced pressure, andwater was added and extracted with ethyl acetate. The organic layer waswashed with brine, dried over anhydrous sodium sulfate and filtered. Thefiltrate was concentrated under reduced pressure and the residue wascrystallized from a mixture of ethyl acetate and diisopropylether togive7-(4-bromo-2,6-dimethylphenyl)-4-hydroxy-2,5-dimethyl-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one(56.6 g).

m.p. 271-273° C.

(4) To a suspension of7-(4-bromo-2,6-dimethylphenyl)-4-hydroxy-2,5-dimethyl-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one(10.0 g) in phosphoryl chloride (25.7 mL) was added N,N-dimethylaniline(2.6 mL) and the mixture was heated at 120° C. for 6 hours. Aftercooling to room temperature the mixture was poured into ice-cold waterand extracted with ethyl acetate. The organic layer was washed with asodium hydrogencarbonate aqueous solution and brine, dried overanhydrous sodium sulfate and filtered. The filtrate was concentratedunder reduced pressure to give a solid. The solid was washed withdiisopropylether to afford7-(4-bromo-2,6-dimethylphenyl)-4-chloro-2,5-dimethyl-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one(8.0 g)

m.p. 148-150° C.

(5) A suspension of7-(4-bromo-2,6-dimethylphenyl)-4-chloro-2,5-dimethyl-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one(7.5 g), ethyl isonipecotate (4.7 g), N,N-diisopropylethylamine (3.8 g)in ethanol (35 mL) was heated at reflux for 12 hours. The reactionmixture was stirred at room temperature to afford a solid. The solid wascollected by filtration and washed with cold ethanol to give1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-4-carboxylicacid ethyl ester (7.7 g).

m.p. 159-161° C.

(6) To a solution of lithium borohydride (2.61 g) in tetrahydrofuran (60mL) was added a solution of1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-4-carboxylicacid ethyl ester (6.0 g) in a mixture of tetrahydrofuran (60 mL) andmethanol (3 mL) dropwise over 10 minutes under ice-cooling. The reactionmixture was warmed up to room temperature and stirred for 3 hours. Aftercooling with an ice-bath, 6 M HCl aqueous solution (30 mL) was added andstirred at room temperature for 1 hour. The solution was made toalkaline (pH=9) with 6 M NaOH aqueous solution, and extracted with ethylacetate. The organic layer was washed with brine, dried over anhydroussodium sulfate and filtered. The filtrate was concentrated under reducedpressure and the residue was purified by a silica gel columnchromatography (silica gel: Wako Gel (C200), eluent: hexane/ethylacetate=1:1) to give{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(4.6 g).

(7) To a suspension of{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(0.71 g) in water (7 mL) was added concentrated HCl aqueous solution(0.15 mL) under ice-cooling. The mixture was stirred at room temperaturefor 5 minutes, cooled with an ice-bath again, and stirred for 15 minutesin an ice-cooling bath. The precipitate was collected by filtration,washed with water and dried to give the title compound (0.73 g).

Example 4 Synthesis of{1-[1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-4-yl}methanolhydrochloride (2-019)

(1) To a solution of2-amino-1-(4-chloro-2,6-dimethylphenyl)-4-methyl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitrile(44.1 g), which was obtained in the same method as example 3, intetrahydrofuran (220 mL) was added isopropenyl methyl ether (46.2 g) andp-toluenesulfonic acid (608 mg). The mixture was heated at reflux for 1hour. After removing the solvent under reduced pressure, the residue wasdissolved in tetrahydrofuran (500 mL) and cooled in an ice-NaCl bath.Lithium diisopropylamide in tetrahydrofuran solution (generated from2.64M n-butyl lithium in hexane (127 mL), diisopropylamine (40.5 g) andtetrahydrofuran (300 mL)) was added dropwise over 30 minutes, andstirred at room temperature for 1 hour. To the reaction mixture asaturated NH₄Cl aqueous solution was added and separated. The aqueouslayer was extracted with CHCl₃. The organic layer was washed with water,dried over anhydrous sodium sulfate and filtered. The filtrate wasconcentrated under reduced pressure and the residue was purified by asilica gel column chromatography (silica gel: Wako Gel (C200), eluent:hexane/ethyl acetate=1:1) to give4-amino-1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1,3-dihydropyrrolo[2,3-b]pyridin-2-one(35.8 g) as an amorphous.

MS (ES, Pos.): 316 (M+1)⁺, 318 (M+3)⁺, 338 (M+Na)⁺, 340 (M+Na+2)⁺

(2) To a suspension of lithium borohydride (11.6 g) in tetrahydrofuran(50 mL) was added a solution of4-amino-1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1,3-dihydropyrrolo[2,3-b]pyridin-2-one(33.7 g) in tetrahydrofuran (100 mL) was added. The mixture was stirredat reflux for 1 hour. After cooling with ice-cooling bath, a 6M HClaqueous solution was added slowly. The solution was made to alkaline(pH=9) with 4 M NaOH aqueous solution, and extracted with ethyl acetate.The organic layer was washed with brine, dried over anhydrous sodiumsulfate and filtered. The filtrate was concentrated under reducedpressure and the residue was purified by a silica gel columnchromatography (silica gel: Wako Gel (C200), eluent: hexane/ethylacetate=3:1) to give1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ylamine(17.9 g) as a solid.

m.p. 190-192° C.

(3) With ice-cooling, to a suspension of1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ylamine(17.9 g) in a mixture of 1,4-dioxane (45 mL) and water (45 mL) was addeddropwise a mixture of concentrated H₂SO₄ (17.8 mL) and water (90 mL) andthen a solution of NaNO₂ (6.2 g) in water (62 mL). The mixture wasstirred at room temperature for 20 minutes, and heated at 100° C. for1.5 hours. After cooling in an ice-cooling bath, the reaction mixturewas poured into a cold saturated NaHCO₃ aqueous solution and extractedwith CHCl₃. The organic layer was dried over anhydrous sodium sulfate,and filtered. The filtrate was concentrated under reduced pressure togive a solid. The solid was washed with a mixture of ethyl acetate anddiisopropylether (1:5) to give1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ol(14.4 g).

m.p. 260° C. (decomp.)

(4) To a mixture of1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ol(14.4 g) and triethylamine (9.7 g) in CHCl₃ (100 mL) was addedtrifluoromethansulfonic anhydride (9.7 mL) in an ice-cooling bath. Afterstirring for 10 minutes, water was added and extracted with CHCl₃. Theorganic layer was washed with water and brine successively, dried overanhydrous sodium sulfate and filtered. The filtrate was concentratedunder reduced pressure to give crude trifluoromethanesulfonic acid1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ylester (20.7 g).

A mixture of the crude trifluoromethanesulfonic acid1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ylester (20.5 g), ethyl isonipecotate (74.4 g) andN,N-diisopropylethylamine (12.2 g) was heated at 150-170° C. for 1 hour.To the reaction mixture, water was added and extracted with ethylacetate. The organic layer was washed with water, and brine, dried overanhydrous sodium sulfate and filtered. The filtrate was concentratedunder reduced pressure and the residue was purified by a silica gelcolumn chromatography (silica gel: Wako Gel (C200), eluent: hexane/ethylacetate=5:1) to give1-[1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidine-4-carboxylicacid ethyl ester (16.6 g) as a pale yellow solid.

m.p. 140-142° C.

(5) To a suspension of lithium borohydride (4.11 g) in tetrahydrofuran(50 mL) was added a solution of1-[1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidine-4-carboxylicacid ethyl ester (16.6 g) in a mixture of tertrahydrofuran (80 mL) andmethanol (7.7 mL) in an ice-cooling bath. The mixture was stirred atroom temperature for 2 hours. After cooling with an ice-cooling bath,water was added and the mixture was poured slowly into a 3M HCl aqueoussolution. The solution was made to alkaline (pH=8) with 4 M NaOH aqueoussolution to give a solid. The solid was collected by filtration andwashed with water and diethylether. The solid was recrystallized from amixture of ethanol and ethyl acetate to give{1-[1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-4-yl}methanol(9.1 g).

(6) In the same method as example 1-(2), the title compound (8.0 g) wasobtained from{1-[1-(4-chloro-2,6-dimethylphenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-4-yl}methanol(9.1 g).

Example 5 Synthesis of carbonic acid1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethylester ethyl ester (3-001)

{1-[7-(4-Bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(1.15 g) synthesized in the similar manner as example 1 intetrahydrofuran (25 mL) was stirred, then NaH (60% in paraffin, 0.10 g)was added and the mixture was healed at reflux for 3 hours. Aftercooling to 0° C., ethyl chloroformate (0.28 g) in a small amount oftetrahydrofuran was added and the reaction mixture was allowed to reachroom temperature and evaporated. The residue was purified over a silicagel on a glass filter (eluent: CH₂Cl₂/CH₃CN=95:5 then 90:10) to give thetitle product (366 mg).

Table 3 lists the compound obtained in Example 5 and compounds obtainedby the similar procedure as in Example 5.

Example 6 Synthesis of decanoic acid1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethylester (3-009)

Under nitrogen atmosphere,{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(1.15 g) synthesized in the similar manner as example 1 intetrahydrofuran (25 mL) was stirred, then NaH (60% in paraffin, 0.10 g)was added and the mixture was heated at reflux overnight, giving mixture(I). Decanoic acid (0.45 g) in tetrahydrofuran (25 mL) was stirred, then1,1′-carbonyldiimidazole (0.42 g) was added and the mixture was stirredovernight at room temperature, giving mixture (II). The mixture (II) wasadded dropwise to the mixture (I) at 0-5° C. and the resulting reactionmixture was allowed to reach room temperature. The solvent wasevaporated and the residue was purified over a silica gel on a glassfilter (eluent: CH₂Cl₂/CH₃CN=100:0, 95:5 then 90:10) to give the titleproduct (888 mg).

Table 3 lists the compound obtained in Example 6 and compounds obtainedby the similar procedure as in Example 6.

Example 7 Synthesis of eicosa-5,8,11,14-tetraenoic acid1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethylester (3-020)

Under nitrogen atmosphere, to a solution of1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(606 mg) in CH₂Cl₂ (20 ml) was added arachidonic acid (500 mg),4-dimethylaminopyridine (33 mg) and N,N′-dicyclohexylcarbodiimide (565mg). The mixture was stirred at room temperature for 2 hours andconcentrated under reduced pressure. The residue was purified by asilica gel column chromatography (silica gel: Wako Gel (C200), eluent:hexane/ethyl acetate=7:1) to give the title compound (990 mg) as an oil.

Table 3 lists the compound obtained in Example 7 and compounds obtainedby the similar procedure as in Example 7.

Example 8 Synthesis of(S)-2-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-propionic acid1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethylester (3-014) and (S)-2-amino-3-(1H-indol-3-yl)-propionic acid1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethylester (3-016)

(1) A solution of N-(tert-butoxycarbonyl)-L-tryptophan (510 mg) and1,1′-carbonyldiimidazole (330 mg) in acetonitrile (10 mL) was stirred atroom temperature overnight. The solvent is evaporated and the residue isredissolved in toluene (5 mL). Sequentially{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(594 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (40 μL) were added andstirred at room temperature for 2 days. After evaporation of the solventthe residue was extracted with ethylacetate and dilute NaHCO₃ solution.After the usual work-up the residue of the extract was purified oversilica gel (eluent: CH₂Cl₂/MeOH=95:5) to give the title product 3-014(578 mg).

(2) To a solution of 3-014 (1.16 g) in CH₂Cl₂ (200 mL) a 6M solution ofHCl in isopropanol (2.7 mL) was added and stirred at room temperaturefor 2 days. After evaporation, the residue is purified by reversed-phasechromatography (BDS RP18, 8 μm particle size, 200 g, ID 5 cm column,eluent: (0.5% NH₄Ac/CH₃CN: 9:1 (v/v)) CH₃CN 85/15 to 1/9 gradient).After partial evaporation of the aqueous fractions a fine precipitate ofpure compound is formed and recuperated, yielding the tittle compound3-016 (139 mg). The aqueous filtrate was extracted with CH₂Cl₂ and theorganic extract was washed with dilute ammonia. After the usual work-upof the organic extract some more product 3-016 was recuperated (304 mg).

Example 9 Synthesis of phosphoric acid1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethylester diethyl ester (3-017)

Under nitrogen atmosphere, to a solution of{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol(0.50 g) and 4-dimethylaminopyridine (0.55 g) in CH₂Cl₂ (50 mL) at 0° C.diethyl chlorophosphate (0.38 g) was added dropwise and the reaction isslowly heated up to room temperature. The reaction mixture is poured onice-water and extracted with CH₂Cl₂. After the usual work-up the residueis purified over silica gel on a glass filter (eluent: CH₂Cl₂/MeOH=98:2)yielding product 3-017 (0.31 g).

Example 10 Synthesis of phosphoric acidmono-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-ylmethyl}ester(3-018)

{1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methyldiphenoxyphosphate ester (1.8 g), which was produced in a similar way asin example 9, was dissolved in 50% NaOH (1 mL) and dioxane (50 mL) andstirred at 60° C. for several hours until completion of the hydrolysis.The solution was treated with water (25 mL), acidified with HCl untilpH=2 and extracted five times with portions CH₂Cl₂, using NaCl toimprove the phase separation. After the usual work-up the residue ispurified over silica gel on a glass filter (eluent: CH₂Cl₂/MeOH=9:1 topure MeOH) yielding the title product 3-018 (0.38 g).

TABLE 1*¹

Com. No. Ex. No.

R⁶ R⁷ R⁸ —Ar melting point (° C.) (solvent for crystallization) 1-001 1

CH₃ CH₃ CH₃

142-144 (hexane) 1-002 1

CH₃ CH₃ H

124-126 (hexane) 1-003 1

CH₃ CH₃ CH₃

amorphous 1-004 1

CH₃ CH₃ CH₃

146-148*² (EtOAc/EtOH) 1-005 1

CH₃ CH₃ H

amorphous 1-006 1

CH₃ CH₃ CH₃

144-146 (hexane) 1-007 1

CH₃ CH₃ H

121-122 (hexane) 1-008 1

CH₃ CH₃ H

141-143*² (EtOAc/EtOH) 1-009 1

CH₃ CH₃ CH₃

134-136*² (EtOAc/EtOH) 1-010 1

CH₃ CH₃ H

157-159*² (EtOAc/EtOH) 1-011 1

CH₃ CH₃ CH₃

amorphous 1-012 1

CH₃ CH₃ H

amorphous 1-013 1

CH₃ CH₃ H

amorphous*³ 1-014 1

CH₃ CH₃ H

amorphous*³ 1-015 1

CH₃ CH₃ CH₃

amorphous 1-016 1

CH₃ CH₃ CH₃

amorphous 1-017 1

CH₃ CH₃ CH₃

144-146*²*⁴ (EtAc/EtOH) 1-018 1

CH₃ CH₃ CH₃

131-133*²*⁴ (EtOAc/EtOH) 1-019 1

CH₃ CH₃ H

amorphous 1-020 1

CH₃ CH₃ H

152-154*²*⁴ (EtOAc/EtOH) 1-021 1

CH₃ CH₃ H

145-147*²*⁴ (EtOAc) 1-022 1

CH₃ CH₃ CH₃

amorphous*³ 1-023 1

CH₃ CH₃ H

amorphous 1-024 1

CH₃ CH₃ CH₃

amorphous 1-025 1

CH₃ CH₃ H

amorphous 1-026 1

CH₃ CH₂CH₃ CH₂CH₃

amorphous 1-027 1

CH₃ CH₃ CH₃

amorphous*³ 1-028 1

CH₃ —(CH₂)₄—

amorphous 1-029 1

CH₃ —CH═CH—CH═CH—

amorphous 1-030 1

CH₃ CH₃ CH₃

amorphous 1-031 1

CH₃ CH₃ H

amorphous 1-032 1

CH₃ CH₃ H

159-161*² (EtOAc/EtOH) 1-033 1

CH₃ CH₃ CH₃

163-164*² (EtOAc/EtOH) 1-034 1

CH₃ CH₃ H

160-162*² (EtOAc/EtOH) 1-035 1

CH₃ CH₃ H

157-159*² (EtOAc/EtOH) 1-036 1

CH₃ CH₃ CH₃

amorphous 1-037 1

CH₃ CH₃ H

amorphous 1-038 1

CH₃ CH₃ CH₃

159-161 (IPE) 1-039 1

CH₃ CH₃ CH₃

amorphous 1-040 1

CH₃ CH₃ H

amorphous 1-041 1

CH₃ CH₂CH₃ CH₂CH₃

amorphous 1-042 1

CH₃ —(CH₂)₄—

134-136*⁵ 1-043 1

CH₃ —CH═CH—CH═CH—

amorphous 1-044 1

CH₃ CH₃ CH₃

amorphous 1-045 1

CH₃ CH₃ H

amorphous 1-046 1

CH₃ CH₃ H

172-174*² (EtOAc/EtOH) 1-047 1

CH₃ CH₃ CH₃

150-152*² (EtOAc/EtOH) 1-048 1

CH₃ CH₃ H

177-179*² (EtOAc/EtOH) 1-049 1

CH₃ CH₃ H

156-158*² (EtOAc/EtOH) 1-050 1

CH₃ CH₃ CH₃

170-172 (hexane) 1-051 1

CH₃ CH₃ H

178-180 (hexane) 1-052 1

CH₃ CH₃ CH₃

157-159 (IPE/hexane) 1-053 1

CH₃ CH₃ CH₃

167-169*² (EtOAc) 1-054 1

CH₃ CH₃ H

173-175*² (EtOH) 1-055 1

CH₃ —(CH₂)₄—

177-179 (IPE) 1-056 1

CH₃ —CH═CH—CH═CH—

amorphous 1-057 1

CH₃ CH₃ CH₃

amorphous 1-058 1

CH₃ CH₃ H

166-168*² (EtOAc) 1-059 1

CH₃ CH₃ CH₃

155-157*² (EtOAc) 1-060 1

CH₃ CH₃ H

176-178*² (EtOAc) 1-061 1

CH₃ CH₃ CH₃

164-166*² (EtOAc) 1-062 1

CH₃ CH₃ H

170-172*² (EtOAc) 1-063 1

CH₃ CH₃ CH₃

amorphous*² 1-064 1

CH₃ CH₃ H

164-166*² (EtOAc) 1-065 1

CH₃ CH₃ CH₃

188-190*² (EtOAc) 1-066 1

CH₃ CH₃ H

184-186*² (EtOAc) 1-067 1

CH₃ CH₃ CH₃

179-181*² (EtOAc) 1-068 1

CH₃ CH₃ H

178-180*² (EtOAc) 1-069 1

CH₃ CH₃ H

197-199*² (EtOAc/EtOH) 1-070 1

CH₃ CH₃ CH₃

155-157*² (EtOAc) 1-071 1

CH₃ CH₃ H

167-169*² (EtOAc/EtOH) 1-072 1

CH₃ CH₃ CH₃

220-222 (hexane) 1-073 1

CH₃ CH₃ CH₃

212-214*² (EtOAc) 1-074 1

CH₃ CH₃ H

187-189*² (EtOAc) 1-075 1

CH₃ CH₃ CH₃

180-182*² (hexane) 1-076 1

CH₃ CH₃ H

188-190*² (IPE) 1-077 1

CH₃ CH₃ CH₃

179-181*² (EtOAc/EtOH) 1-078 1

CH₃ CH₃ H

194-196*² (EtOAc/EtOH) 1-079 1

CH₃ CH₃ CH₃

199-201*² (EtOAc/EtOH) 1-080 1

CH₃ CH₃ H

193-195*² (EtOAc/EtOH) 1-081 1

CH₃ CH₃ CH₃

164-166*² (EtOAc/EtOH) 1-082 1

CH₃ CH₃ H

177-179*² (EtOAc/EtOH) 1-083 1

CH₃ CH₃ CH₃

170-172*² (EtOAc/EtOH) 1-084 1

CH₃ CH₃ H

162-164*² (EtOAc) 1-085 1

CH₃ CH₃ CH₃

168-170*² (EtOAc) 1-086 1

CH₃ CH₃ H

187-189*² (EtOAc/EtOH) 1-087 1

CH₃ CH₃ CH₃

183-184 (hexane) 1-088 1

CH₃ CH₃ H

165-167 (hexane) 1-089 1

CH₃ CH₃ CH₃

191-193 (IPA) 1-090 1

CH₃ CH₃ CH₃

189-191*² (THF/EtOAc) 1-091 1

CH₃ CH₃ H

202-204*² (EtOAc/EtOH) 1-092 1

CH₃ CH₂CH₃ CH₂CH₃

amorphous 1-093 1

CH₃ —(CH₂)₄—

177-179 (IPE) 1-094 1

CH₃ —CH═CH—CH═CH—

amorphous 1-095 1

CH₃ CH₃ CH₃

175-177*² (hexane) 1-096 1

CH₃ CH₃ H

174-176*² (EtOAc) 1-097 1

CH₃ CH₃ H

207-209*² (EtOAc/EtOH) 1-098 1

CH₃ CH₃ CH₃

205-207*² (EtOAc/EtOH) 1-099 1

CH₃ CH₃ H

195-197*² (EtOAc/EtOH) 1-100 1

CH₃ CH₃ H

192-194*² (EtOAc/EtOH) 1-101 1

CH₃ CH₃ CH₃

175-177*² (EtOAc) 1-102 1

CH₃ CH₃ H

158-160*² (EtOAc/EtOH) 1-103 1

CH₃ CH₃ CH₃

amorphous 1-104 1

CH₃ CH₃ CH₃

amorphous 1-105 1

CH₃ CH₃ H

amorphous 1-106 1

CH₃ CH₃ CH₃

amorphous 1-107 1

CH₃ CH₃ H

amorphous 1-108 1

CH₃ CH₃ CH₃

206-208 (IPE) 1-109 1

CH₃ CH₃ H

161-163 (IPE) 1-110 1

CH₃ CH₃ CH₃

amorphous 1-111 1

CH₃ CH₃ H

141-143 (IPE) 1-112 1

CH₃ CH₃ CH₃

184-186*² (EtOH) 1-113 1

CH₃ CH₃ H

181-182 (IPE) 1-114 1

CH₃ CH₃ CH₃

amorphous 1-115 1

CH₃ CH₃ CH₃

167-169*²*⁴ (EtOAc) 1-116 1

CH₃ CH₃ H

amorphous*²*⁴ 1-117 1

CH₃ CH₃ CH₃

148-150*²*⁴ (EtOAc) 1-118 1

CH₃ CH₃ H

amorphous*²*⁴ 1-119 1

CH₃ CH₃ CH₃

214-216*² (EtOAc) 1-120 1

CH₃ CH₃ H

153-155*² (EtOH/EtOAc) 1-121 1

CH₃ CH₃ CH₃

214-215*² (EtOAc) 1-122 1

CH₃ CH₃ H

148-150*² (EtOH/EtOAc) 1-123 1

CH₃ CH₃ CH₃

170-172*² (EtOAc) 1-124 1

CH₃ CH₃ H

91-93*² (EtOH/EtOAc) 1-125 1

CH₃ CH₃ CH₃

amorphous 1-126 1

CH₃ CH₃ H

amorphous 1-127 2

CH₃ CH₃ H

amorphous 1-128 2

CH₃ CH₃ H

amorphous 1-129 1

CH₃ CH₃ CH₃

amorphous 1-130 1

CH₃ CH₃ CH₃

amorphous 1-131 1

CH₃ CH₃ H

amorphous 1-132 1

CH₃ CH₃ CH₃

amorphous*³ 1-133 1

CH₃ CH₃ H

amorphous 1-134 2

CH₃ CH₃ CH₃

amorphous*⁴ 1-135 2

CH₃ CH₃ CH₃

amorphous*⁴ 1-136 2

CH₃ CH₃ CH₃

amorphous*⁴ 1-137 2

CH₃ CH₃ CH₃

amorphous*⁴ 1-138 1

CH₃ CH₃ H

amorphous 1-139 1

CH₃ —(CH₂)₄—

173-175*⁵ 1-140 1

CH₃ —CH═CH—CH═CH—

amorphous 1-141 1

CH₃ CH₃ CH₃

amorphous 1-142 1

CH₃ CH₃ H

amorphous 1-143 1

CH₃ CH₃ CH₃

amorphous 1-144 1

CH₃ CH₃ CH₃

amorphous 1-145 1

CH₃ CH₃ H

147-149 (hexane) 1-146 1

CH₃ CH₃ CH₃

amorphous 1-147 1

CH₃ CH₃ H

amorphous 1-148 1

CH₃ CH₃ CH₃

195-197*² (EtOAc) 1-149 1

CH₃ CH₃ H

amorphous*² 1-150 1

CH₃ CH₃ CH₃

164-166*² (EtOAc) 1-151 1

CH₃ CH₃ H

168-170*² (EtOAc) 1-152 1

CH₃ CH₃ CH₃

145-147*² (EtOAc/IPE) 1-153 1

CH₃ CH₃ CH₃

182-184 (hexane) 1-154 1

CH₃ CH₃ CH₃

166-168*² (IPE) 1-155 1

CH₃ CH₃ H

145-146*² (EtOAc) 1-156 1

CH₃ CH₃ CH₃

164-166*² (EtOAc/IPE) 1-157 1

CH₃ CH₃ H

174-176*² (EtOAc/IPE) 1-158 1

CH₃ CH₃ CH₃

194-196*² (EtOAc) 1-159 1

CH₃ CH₃ H

199-201*² (EtOAc) 1-160 1

CH₃ CH₃ CH₃

162-164*² (EtOAc) 1-161 1

CH₃ CH₃ H

170-172*² (EtOAc) 1-162 1

CH₃ CH₃ CH₃

164-166*² (EtOAc) 1-163 1

CH₃ CH₃ H

152-154*² (EtOAc) 1-164 1

CH₃ CH₃ CH₃

158-160*² (EtOAc) 1-165 1

CH₃ CH₃ H

139-141*² (EtOAc/EtOH) 1-166 1

CH₃ CH₃ CH₃

140-141*² (EtOAc) 1-167 1

CH₃ CH₃ H

137-139*² (EtOAc) 1-168 1

CH₃ CH₃ H

amorphous*² 1-169 1

CH₃ CH₃ CH₃

219-221 (IPE) 1-170 1

CH₃ CH₃ H

179-181 (IPE) 1-171 1

CH₃ CH₃ CH₃

amorphous 1-172 1

CH₃ CH₃ CH₃

269-270 (IPE) 1-173 1

CH₃ CH₃ H

236-238 (IPE) 1-174 1

CH₃ CH₃ CH₃

amorphous 1-175 1

CH₃ CH₃ H

196-198 (IPE) 1-176 1

CH₃ CH₃ CH₃

153-155*² (EtOAc) 1-177 1

CH₃ CH₃ H

205-207*² (EtOAc/EtOH) 1-178 1

CH₃ CH₃ CH₃

182-184*² (EtOAc) 1-179 1

CH₃ CH₃ H

amorphous*² 1-180 1

CH₃ CH₃ CH₃

215-217 (hexane) 1-181 1

CH₃ CH₃ CH₃

150-152*² (EtOAc/EtOH) 1-182 1

CH₃ CH₃ H

121-123*² (EtOAc/EtOH) 1-183 1

CH₃ CH₃ H

125-127*² (EtOAc) 1-184 1

CH₃ CH₃ H

161-163*² (EtOAc/EtOH) 1-185 1

CH₃ CH₃ H

149-151*² (EtOAc/EtOH) 1-186 1

CH₃ CH₃ H

152-154*² (EtOAc/EtOH) 1-187 1

CH₃ CH₃ H

170-172*² (EtOAc/EtOH) 1-188 1

CH₃ CH₃ H

158-160*² (EtOAc) 1-189 1

CH₃ CH₃ H

173-175*² (EtOAc/EtOH) 1-190 1

CH₃ CH₃ H

155-157*² (EtOAc/EtOH) 1-191 1

CH₃ CH₃ H

146-148*² (EtOAc/EtOH) 1-192 1

CH₃ CH₃ H

150-152*² (EtOAc/EtOH) 1-193 1

CH₃ CH₃ H

158-160*² (EtOAc/EtOH) 1-194 1

CH₃ CH₂CH₃ CH₂CH₃

amorphous 1-195 1

CH₃ CH₃ H

177-179*² (EtOAc/EtOH) 1-196 1

CH₃ CH₃ H

154-156*² (EtOAc/EtOH) 1-197 1

CH₃ CH₃ H

153-155*² (EtOAc) 1-198 1

CH₃ CH₃ H

128-130*² (EtOAc/EtOH) 1-199 1

CH₃ CH₃ H

140-142*² (EtOAc) 1-200 1

CH₃ CH₃ H

149-151*² (EtOAc/EtOH) 1-201 1

CH₃ CH₃ H

168-170*² (EtOAc/EtOH) 1-202 1

CH₃ CH₃ H

152-154*² (EtOAc/EtOH) 1-203 1

CH₃ CH₃ H

153-155*² (EtOAc/EtOH) 1-204 1

CH₃ CH₃ H

157-159*² (EtOAc/EtOH) 1-205 1

CH₃ CH₃ H

179-181*² (EtOAc/EtOH) 1-206 1

CH₃ CH₃ H

170-172*² (EtOAc/EtOH) 1-207 1

CH₃ CH₃ H

184-186*² (EtOAc) 1-208 1

CH₃ CH₃ H

172-174*² (EtOAc/EtOH) 1-209 1

CH₃ CH₃ CH₃

amorphous 1-210 1

CH₃ CH₃ H

amorphous 1-211 1

CH₃ CH₃ CH₃

193-195*² (EtOAc) 1-212 1

CH₃ CH₃ H

164-166*² (EtOAc/EtOH) 1-213 1

CH₃ CH₃ CH₃

163-165 (IPE) 1-214 1

CH₃ CH₃ H

182-184 (IPE) 1-215 1

CH₃ CH₃ CH₃

180-182 (EtOAc/EtOH) 1-216 1

CH₃ CH₃ H

153-155 (IPE) 1-217 1

CH₃ CH₃ CH₃

177-179*² (EtOAc) 1-218 1

CH₃ CH₃ H

162-164*² (EtOAc/EtOH) 1-219 1

CH₃ CH₃ H

151-153*² (EtOAc/EtOH) 1-220 1

CH₃ CH₃ CH₃

138-140*² (EtOAc/EtOH) 1-221 1

CH₃ CH₃ H

164-166*² (EtOAc/EtOH) 1-222 1

CH₃ CH₂CH₃ CH₂CH₃

amorphous 1-223 1

CH₃ CH₃ H

129-131*² (EtOAc/IPE) 1-224 1

CH₃ CH₃ H

138-140*² (EtOAc/EtOH) 1-225 1

CH₃ CH₃ H

131-133*² (EtOAc) 1-226 1

CH₃ CH₃ H

205-207*² (EtOAc) 1-227 1

CH₃ CH₃ H

180-182*² (EtOAc) 1-228 1

CH₃ CH₃ H

165-167*² (EtOAc/EtOH) 1-229 1

CH₃ CH₃ H

185-187*² (IPE) 1-230 1

CH₃ CH₃ H

130-132*² (EtOAc/EtOH) 1-231 1

CH₃ CH₃ H

131-133*² (EtOH) 1-232 1

CH₃ CH₃ H

146-148*² (EtOAc/EtOH) 1-233 1

CH₃ CH₃ H

160-162*² (EtOAc/EtOH) 1-234 1

CH₃ CH₃ H

193-195*² (EtOAc/EtOH) 1-235 1

CH₃ CH₃ H

190-192*² (EtOAc/EtOH) 1-236 1

CH₃ CH₃ CH₃

180-182*² (EtOAc/EtOH) 1-237 1

CH₃ CH₃ H

159-161*² (EtOAc/EtOH) 1-238 1

CH₃ CH₃ CH₃

amorphous*⁴ 1-239 1

CH₃ CH₃ CH₃

amorphous*⁴ 1-240 1

CH₃ CH₃ CH₃

amorphous*⁴ 1-241 1

CH₃ CH₃ CH₃

amorphous*⁴ 1-242 1

CH₃ CH₃ H

185-187*² (EtOH) 1-243 1

CH₃ CH₃ H

186-188*² (EtOAc/EtOH) 1-244 1

CH₃ CH₃ H

174-176*² (EtOAc/EtOH) 1-245 1

CH₃ CH₃ H

165-167*² (EtOAc/EtOH) 1-246 1

CH₃ CH₃ H

172-174*² (EtOAc/EtOH) 1-247 1

CH₃ CH₃ H

155-157*² (EtOAc/EtOH) 1-248 1

CH₃ CH₃ H

139-141*² (EtOAc/EtOH) 1-249 1

CH₃ CH₃ H

176-178*² (EtOAc/IPE) 1-250 1

CH₃ CH₃ H

147-149*² (EtOAc) 1-251 1

CH₃ CH₃ CH₃

170-172*² (EtOAc) 1-252 1

CH₃ CH₃ CH₃

193-195 (EtOAc/IPE) 1-253 1

CH₃ CH₃ H

200-202 (IPE) 1-254 1

CH₃ CH₃ CH₃

155-157*² (EtOAc/EtOH) 1-255 1

CH₃ CH₃ CH₃

222-224 (IPE) 1-256 1

CH₃ CH₃ H

193-195 (IPE) 1-257 1

CH₃ CH₃ CH₃

199-201*² (EtOAc/EtOH) 1-258 1

CH₃ CH₃ H

166-168*² (EtOAc/EtOH) 1-259 1

CH₃ CH₃ H

165-167*² (EtOAc/EtOH) 1-260 1

CH₃ CH₃ H

167-169*² (EtOAc) 1-261 1

CH₃ CH₃ H

187-189*² (EtOAc/EtOH) 1-262 1

CH₃ CH₃ H

185-187*² (EtOAc/IPE) 1-263 1

CH₃ CH₃ H

141-143*² (EtOAc) 1-264 1

CH₃ CH₃ CH₃

179-181 (IPE) 1-265 1

CH₃ CH₃ H

218-220 (EtOAc/EtOH) 1-266 1

CH₃ CH₃ CH₃

166-168*² (EtOAc/EtOH) 1-267 1

CH₃ CH₃ H

amorphous*² 1-268 1

CH₃ CH₃ CH₃

158-160*² (EtOAc/EtOH) 1-269 1

CH₃ CH₃ H

160-162*² (EtOAc/EtOH) 1-270 1

CH₃ H H

162-164 (EtOAc/IPE) 1-271 1

CH₃ CH₃ H

133-136*² (EtOAc/EtOH) 1-272 1

CH₃ CH₃ CH₃

229-231 (CH3CN) 1-273 1

CH₃ CH₃ H

208-210 (CH3CN) 1-274 1

CH₃ CH₃ OH

196-198 (EtOH) 1-275 1

CH₃ CH₃ H

129-131*² (EtOAc) 1-276 1

CH₃ CH₃ CH₃

166-168*²*⁴ (EtOAc/EtOH) 1-277 1

CH₃ CH₃ H

131-133*²*⁴ (EtOAc/EtOH) 1-278 1

CH₃ CH₃ CH₃

158-160*²*⁴ (EtOAc/EtOH) 1-279 1

CH₃ CH₃ H

129-131*²*⁴ (EtOAc/EtOH) 1-280 1

CH₃ CH₃ H

144-146*²*⁴ (EtOAc/EtOH) 1-281 1

CH₃ CH₃ H

170-173*²*⁴ (EtOAc/EtOH) 1-282 1

CH₃ CH₃ H

152-155*²*⁴ (EtOAc/EtOH) 1-283 1

CH₃ CH₃ CH₃

184-185*²*⁴ (EtOAc/EtOH) 1-284 1

CH₃ CH₃ H

122-124*²*⁴ (EtOAc/EtOH) 1-285 1

CH₃ CH₃ CH₃

150-152*² (EtOAc/EtOH) 1-286 1

CH₃ CH₃ H

165-167*² (EtOAc/EtOH) 1-287 1

CH₃ CH₃ CH₃

182-184*² (EtOAc/EtOH) 1-288 1

CH₃ CH₃ H

172-174*² (EtOAc/EtOH) 1-289 1

CH₃ CH₃ CH₃

162-165*² (EtOAc/EtOH) 1-290 1

CH₃ CH₃ H

149-151*² (EtOAc/EtOH) 1-291 1

CH₃ CH₃ CH₃

232-234*² (EtOAc/EtOH) 1-292 1

CH₃ CH₃ H

164-166*² (EtOAc/EtOH) 1-293 1

CH₃ CH₃ CH₃

192-194*² (EtOAc/EtOH) 1-294 1

CH₃ CH₃ H

153-155*² (EtOAc/EtOH) 1-295 1

CH₃ CH₃ CH₃

162-164*² (EtOAc) 1-296 1

CH₃ CH₃ H

204-206*² (EtOAc/EtOH) 1-297 1

CH₃ CH₃ H

145-147 (EtOAc/IPE) 1-298 1

CH₃ CH₃ H

195-196 (EtOAc/IPE) 1-299 1

CH₃ CH₃ H

202-203 (EtOAc/IPE) 1-300 1

CH₃ CH₃ CH₃

202-203 (EtOAc/IPE) 1-301 1

CH₃ CH₃ H

181-183 (EtOAc/IPE) 1-302 1

CH₃ CH₃ CH₃

203-205*⁴ (IPE) 1-303 1

CH₃ CH₃ H

156-158*⁴ (IPE) 1-304 1

CH₃ CH₃ CH₃

212-213*⁴ (IPE) 1-305 1

CH₃ CH₃ H

164-166*⁴ (IPE) 1-306 1

CH₃ CH₃ CH₃

188-190 (IPE)*⁴ 1-307 1

CH₃ CH₃ H

191-192 (IPE)*⁴ 1-308 1

CH₃ CH₃ CH₃

188-189 (IPE)*⁴ 1-309 1

CH₃ CH₃ H

190-191 (IPE)*⁴ 1-310 1

CH₃ CH₃ CH₃

200-202 (IPE) 1-311 1

CH₃ CH₃ H

131-133 (IPE) 1-312 1

CH₃ CH₃ CH₃

223-224 (IPE) 1-313 1

CH₃ CH₃ H

184-186 (IPE) 1-314 1

CH₃ CH₃ CH₃

215-216 (IPE) 1-315 1

CH₃ CH₃ H

214-215 (IPE) 1-316 1

CH₃ CH₃ CH₃

amorphous 1-317 1

CH₃ CH₃ CH₃

151-153 (EtOAc) 1-318 1

CH₃ CH₃ H

149-151 (IPE) 1-319 1

CH₃ CH₃ CH₃

240-242*² (EtOAc/EtOH) 1-320 1

CH₃ CH₃ H

216-218*² (EtOAc/EtOH) 1-321 1

CH₃ CH₃ CH₃

180-183*² (EtOAc/EtOH) 1-322 1

CH₃ CH₃ H

214-216*² (EtOAc/EtOH) 1-323 1

CH₃ CH₃ CH₃

198-200*² (EtOAc/EtOH) 1-324 1

CH₃ CH₃ H

291-293*² (EtOAc/EtOH) 1-325 1

CH₃ CH₃ CH₃

amorphous 1-326 1

CH₃ CH₃ CH₃

183-186*² (EtOAc/EtOH) 1-327 1

CH₃ CH₃ H

154-156*² (EtOAc/EtOH) 1-328 1

CH₃ CH₃ CH₃

192-194 (No solvent) 1-329 1

CH₃ H H

156-158*²*⁵ 1-330 1

CH₃ CH₃ H

159-161*² (IPE) 1-331 1

CH₃ CH₃ OH

242-244*⁵ 1-332 1

CH₃ CH₃ CH₃

217-219*² (EtOAc/EtOH) 1-333 1

CH₃ CH₃ H

204-206*² (EtOAc/EtOH) 1-334 1

CH₃ CH₃ CH₃

143-145*² (EtOAc/EtOH) 1-335 1

CH₃ CH₃ H

172-174*² (EtOAc/EtOH) 1-336 1

CH₃ CH₃ CH₃

168-170 (IPE/hexane) 1-337 1

CH₃ CH₃ H

164-166 (IPE) 1-338 1

CH₃ CH₃ CH₃

amorphous 1-339 1

CH₃ CH₃ H

amorphous 1-340 1

CH₃ CH₃ CH₃

148-150 (IPE) 1-341 1

CH₃ CH₃ CH₃

183-185 (IPE) 1-342 1

CH₃ CH₃ CH₃

221-223 (EtOAc) 1-343 1

CH₃ CH₃ H

205-206 (EtOAc) 1-344 1

CH₃ CH₃ H

203-204 (EtOAc) 1-345 1

CH₃ CH₃ H

196-198 (EtOAc) 1-346 1

CH₃ CH₃ CH₃

234-236 (EtOAc) 1-347 1

CH₃ CH₃ H

202-236 (EtOAc) 1-348 1

CH₃ CH₃ H

187-188 (EtOAc) 1-349 1

CH₃ CH₃ H

200-201 (EtOAc)

*1: Com. No.=compound number, Ex. No.=example number, solvent forcrystallation; EtOAc=ethyl acetate, EtOH=ethanol, IPE=diisopropylether,THF=tetrahydrofuran, IPA=isopropyl alcohol, ACE=acetone,CH3CN=acetonitrile

Analytical data of non-crystal compounds, diastereoisomers and opticallyactive compounds are described below.

1-003:

MS (ES, Pos.): 589 (M+1)⁺, 591 (M+3)⁺, 593 (M+5)⁺, 611 (M+Na), 613(M+Na+2)⁺, 615 (M+Na+4)⁺; HPLC retention time: 4.84 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-005:

MS (ES, Pos.): 457 (M+1)⁺, 459 (M+3)⁺, 479 (M+Na)⁺, 481 (M+Na+2)⁺; HPLCretention time: 9.47 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-011:

MS (ES, Pos.): 393 (M+1)⁺, 415 (M+Na)⁺; HPLC retention time: 4.16 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-012:

MS (ES, Pos.): 379 (M+1)⁺, 401 (M+Na); HPLC retention time: 3.8 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-013:

MS (ES, Pos.): 523 (M+1)⁺, 525 (M+3)⁺, 527 (M+5)⁺, 545 (M+Na)⁺, 547(M+Na+2)⁺, 549 (M+Na+4)⁺; HPLC retention time: 3.14 and 3.27 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-014:

MS (ES, Pos.): 539 (M+1)⁺, 541 (M+3)⁺, 543 (M+5)⁺, 561 (M+Na)⁺, 563(M+Na+2)⁺, 565 (M+Na+4)⁺; HPLC retention time: 3.57 and 3.69 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20); pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-015:

MS (ES, Pos.): 575 (M+1)⁺, 577 (M+3)⁺, 579 (M+5)⁺; HPLC retention time:4.05 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-016:

MS (ES, Pos.): 457 (M+1)⁺, 459 (M+3)⁺, 479 (M+Na)⁺, 481 (M+Na+2)⁺; HPLCretention time: 4.60 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-017 (the Enantiomer of 1-018):

HPLC retention time: 10.0 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)

1-018 (the Enantiomer of 1-017):

HPLC retention time: 11.4 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)

1-019:

MS (ES, Pos.): 443 (M+1)⁺, 466 (M+Na); HPLC retention time: 4.27 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-020 (the Enantiomer of 1-021):

HPLC retention time: 9.1 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)

1-021 (the Enantiomer of 1-020):

HPLC retention time: 11.0 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)1-022:

MS (ES, Pos.): 439 (M+1)⁺, 461 (M+Na)⁺; HPLC retention time: 4.27 and4.56 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-023:

MS (ES, Pos.): 425 (M+1)⁺, 447 (M+Na)⁺; HPLC retention time: 4.16 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-024:

MS (ES, Pos.): 497 (M+1)⁺, 499 (M+3)⁺, 519 (M+Na)⁺, 521 (M+Na+2)⁺; HPLCretention time: 3.72 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-025:

MS (ES, Pos.): 483 (M+1)⁺, 485 (M+3)⁺, 505 (M+Na)⁺, 507 (M+Na+2)⁺; HPLCretention time: 3.66 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-026:

MS (ES, Pos.): 421 (M+1)⁺; HPLC retention time: 5.20 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-027:

MS (ES, Pos.): 409 (M+1)⁺, 431 (M+Na)⁺; HPLC retention time: 2.70 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-028:

MS (ES, Pos.): 419 (M+1)⁺; HPLC retention time: 5.45 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-029:

MS (ES, Pos.): 415 (M+1)⁺; HPLC retention time: 5.27 mini (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-030:

MS (ES, Pos.): 485 (M+1)⁺, 487 (M+3)⁺, 507 (M+Na)⁺, 509 (M+Na+2)⁺; HPLCretention time: 8.57 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-031:

MS (ES, Pos.): 471 (M+1)⁺, 473 (M+3)⁺, 493 (M+Na)⁺, 495 (M+Na+2)⁺; HPLCretention time: 7.71 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-036:

MS (ES, Pos.): 407 (M+1)⁺, 429 (M+Na)⁺; HPLC retention time: 4.32 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-037:

MS (ES, Pos.): 415 (M+Na)⁺; HPLC retention time: 3.98 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-039:

MS (ES, Pos.): 471 (M+1)⁺, 473 (M+3)⁺, 493 (M+Na)⁺, 495 (M+Na+2)⁺; HPLCretention time: 4.91 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-040:

MS (ES, Pos.): 479 (M+Na)⁺, 481 (M+Na+2)⁺; HPLC retention time: 4.46min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-041:

MS (ES, Pos.): 435 (M+1)⁺; HPLC retention time: 5.56 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-043:

MS (ES, Pos.): 429 (M+1)⁺; HPLC retention time: 5.47 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-044:

MS (ES, Pos.): 499 (M+1)⁺, 501 (M+3)⁺; HPLC retention time: 6.66 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-045:

MS (ES, Pos.): 485 (M+1)⁺, 487 (M+3)⁺, 507 (M+Na)⁺, 509 (M+Na+2)⁺; HPLCretention time: 6.89 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-056:

MS (ES, Pos.): 415 (M+1)⁺; HPLC retention time: 4.45 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-057:

MS (ES, Pos.): 485 (M+1)⁺, 487 (M+3)⁺; HPLC retention time: 7.54 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-063:

MS (ES, Pos.): 571 (M+Na), 573 (M+Na+2)⁺, 575 (M+Na+4)⁺; HPLC retentiontime: 5.20 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate:1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-092:

MS (ES, Pos.): 449 (M+1)⁺; HPLC retention time: 6.24 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-094:

MS (ES, Pos.): 443 (M+1)⁺; HPLC retention time: 6.22 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-103:

MS (ES, Pos.): 589 (M+1)⁺, 591 (M+3)⁺, 593 (M+5), 611 (M+Na), 613(M+Na+2)⁺, 615 (M+Na+4)⁺; HPLC retention time: 5.01 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-104:

MS (ES, Pos.): 471 (M+1)⁺, 473 (M+3)⁺, 493 (M+Na), 495 (M+Na+2)⁺; HPLCretention time: 6.69 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-105:

MS (ES, Pos.): 457 (M+1)⁺, 459 (M+3)⁺, 479 (M+Na)⁺, 481 (M+Na+2)⁺; HPLCretention time: 6.01 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-106:

MS (ES, Pos.): 499 (M+1)⁺, 501 (M+3)⁺, 521 (M+Na)⁺, 523 (M+Na+HPLCretention time: 8.06 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-107:

MS (ES, Pos.): 485 (M+1)⁺, 487 (M+3)⁺, 507 (M+Na)⁺, 509 (M+Na+2)⁺; HPLCretention time: 10.24 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-110:

MS (ES, Pos.): 501 (M+1)⁺, 503 (M+3)⁺, 523 (M+Na)⁺, 525 (M+Na+2)⁺; HPLCretention time: 4.61 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-114:

MS (ES, Pos.): 613 (M+Na)⁺, 615 (M+Na+2)⁺, 617 (M+Na+4)⁺; HPLC retentiontime: 2.57 min (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate:1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-115:

HPLC retention time: 10.6 mM. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)

1-116:

MS (ES, Pos.): 451 (M+NO % 453 (M+Na+2)⁺; HPLC retention time: 11.5 min.(CHIRAL PAK AD (DAICEL CHEMICAL INDUSTRIES, LTD), 0.46 cm I.D.×25 cm,mobile phase: hexane/IPA=20:1, flow rate: 1.0 mL/min.)

1-117:

HPLC retention time: 9.3 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)

1-118:

MS (ES, Pos.): 429 (M+1)⁺, 431 (M+3)⁺; HPLC retention time: 12.1 min.(CHIRAL PAK AD (DAICEL CHEMICAL INDUSTRIES, LTD), 0.46 cm I.D.×25 cm,mobile phase: hexane/IPA=20:1, flow rate: 1.0 mL/min.)

1-125:

MS (ES, Pos.): 388 (M+1)⁺, 410 (M+Na)⁺; HPLC retention time: 4.20 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-126:

MS (ES, Pos.): 396 (M+Na); HPLC retention time: 4.40 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile 10.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-127 (a Diastereoisomer of 1-128):

Rf value 0.55 (developing solvent: hexane/EtOAc=1:1, TLC plate Silicagel 60 F₂₅₄ (Merck)); ¹H NMR (300 MHz, CDCl₃) δ 1.64-1.82 (1H, m),1.83-2.03 (2H, m), 2.05-2.18 (1H, m), 2.34 (3H, s), 2.46 (3H, m), 2.53(3H, s), 2.99-3.12 (1H, m), 3.31-3.70 (3H, m), 3.90-4.02 (1H, m), 6.63(1H, s), 7.30 (1H, d, J=2.0 Hz), 7.62 (1H, d, J=2.0 Hz); MS (ES, Pos.):556 (M+Na), 558 (M+Na+2), 560 (M+Na+4)⁴.

1-128 (a Diastereoisomer of 1-127):

Rf value 0.48 (developing solvent: hexane/EtOAc=1:1, TLC plate Silicagel 60 F₂₅₄ (Merck)); ¹H NMR (300 MHz, CDCl₃) δ 1.62-1.81 (1H, m),1.89-2.03 (2H, m), 2.05-2.19 (1H, m), 2.35 (3H, s), 2.46 (3H, d, J=1.2Hz), 2.53 (3H, s), 3.01-3.13 (1H, m), 3.34-3.70 (3H, m), 3.91-4.02 (1H,m), 6.63 (1H, s), 7.30 (1H, d, J=2.0 Hz), 7.62 (1H, d, J=2.0 Hz); MS(ES, Pos.): 534 (M+1)⁺, 536 (M+3)⁺, 538 (M+5)⁺, 556 (M+Na)⁺, 558(M+Na+2), 560 (M+Na+4)⁺

1-129:

MS (ES, Pos.): 570 (M+1)⁺, 572 (M+3)⁺, 574 (M+5)⁺; HPLC retention time:4.46 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-130:

MS (ES, Pos.): 452 (M+1)⁺, 454 (M+3)⁺, 474 (M+Na)⁺, 476 (M+Na+2)⁺; HPLCretention time: 5.36 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-131:

MS (ES, Pos.): 460 (M+Na)⁺, 462 (M+Na+2)⁺; HPLC retention time: 4.87min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-132:

MS (ES, Pos.): 456 (M+Na)⁺; HPLC retention time: 5.12 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-133:

MS (ES, Pos.): 442 (M+Na)⁺; HPLC retention time: 4.64 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-138:

MS (ES, Pos.): 500 (M+Na)⁺, 502 (M+Na+2)⁺; HPLC retention time: 4.05min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-140:

MS (ES, Pos.): 410 (M+1)⁺; HPLC retention time: 5.85 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-141:

MS (ES, Pos.): 480 (M+1)⁺, 482 (M+3)⁺, 502 (M+Na)⁺, 504 (M+Na+2)⁺; HPLCretention time: 7.51 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-142:

MS (ES, Pos.): 466 (M+1)⁺, 468 (M+3)⁺, 488 (M+Na)⁺, 490 (M+Na+2)⁺; HPLCretention time: 9.01 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-143:

MS (ES, Pos.): 584 (M+1)⁺, 586 (M+3)⁺, 588 (M+5)⁺, 606 (M+Na)⁺, 608(M+Na+2)⁺, 610 (M+Na+4)⁺; HPLC retention time: 4.48 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-144:

MS (ES, Pos.): 466 (M+1)⁺, 468 (M+3)⁺, 488 (M+Na)⁺, 490 (M+Na+2)⁺; HPLCretention time: 5.92 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-146:

MS (ES, Pos.): 516 (M+Na)⁺, 518 (M+Na+2)⁺; HPLC retention time: 8.63min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-147:

MS (ES, Pos.): 480 (M+1)⁺, 482 (M+3)⁺, 502 (M+Na)⁺, 504 (M+Na+2)⁺; HPLCretention time: 3.44 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-149:

MS (ES, Pos.): 466 (M+1)⁺, 468 (M+3)⁺, 488 (M+Na)⁺, 490 (M+Na+2)⁺

1-168:

MS (ES, Pos.): 444 (M+1)⁺, 466 (M+Na)⁺; HPLC retention time: 4.11 min.(Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min;Mobile phase: acetonitrile/0.05M ammonium acetate aqueous solution(80:20), pH of the solvent was adjusted to 7.4 with aqueous ammonia oracetic acid.

1-171:

MS (ES, Pos.): 596 (M+1)⁺, 598 (M+3)⁺, 600 (M+5)⁺, 618 (M+Na)⁺, 620(M+Na+2)⁺, 622 (M+Na+4)⁴″; HPLC retention time: 5.87 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-174:

MS (ES, Pos.): 506 (M+1)⁺, 508 (M+3)⁺, 528 (M+Na)⁺, 530 (M+Na+2)⁺; HPLCretention time: 5.83 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-179:

MS (ES, Pos.): 474 (M+Na)⁺, 476 (M+Na+2)⁺; HPLC retention time: 5.74min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0ml/min; Mobile phase: acetonitrile/0.05M ammonium acetate aqueoussolution (80:20), pH of the solvent was adjusted to 7.4 with aqueousammonia or acetic acid.

1-194:

MS (ES, Pos.): 421 (M+1)⁺; HPLC retention time: 5.08 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-209:

MS (ES, Pos.): 496 (M+1)⁺

1-210:

MS (ES, Pos.): 482 (M+1)⁺

1-222:

MS (ES, Pos.): 421 (M+1)⁺; HPLC retention time: 7.13 min. (Capcell PakUG120, 4.6 mm×150 mm, Shiseido); Flow rate: 1.0 ml/min; Mobile phase:acetonitrile/0.05M ammonium acetate aqueous solution (80:20), pH of thesolvent was adjusted to 7.4 with aqueous ammonia or acetic acid.

1-238:

MS (ES, Pos.): 575 (M+1)⁺, 577 (M+3)⁺, 579 (M+5)⁺

HPLC retention time: 8.6 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)1-239:

MS (ES, Pos.): 575 (M+1)⁺, 577 (M+3)⁺, 579 (M+5)⁺

HPLC retention time: 9.6 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=20:1,flow rate: 1.0 mL/min.)1-240:

MS (ES, Pos.): 570 (M+1)⁺, 572 (M+3)⁺, 574 (M+5)⁺

HPLC retention time: 13.0 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=100:1,flow rate: 1.0 mL/min.)1-241:

MS (ES, Pos.): 570 (M+1)⁺, 572 (M+3)⁺, 574 (M+5)⁺

HPLC retention time: 11.9 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=100:1,flow rate: 1.0 mL/min.)1-267:

MS (ES, Pos.): 438 (M 1)⁺, 440 (M+3)⁺, 460 (M+Na)⁺, 462 (M+Na+2)⁺; HPLCretention time: 4.43 min. (Capcell Pak UG120, 4.6 mm×150 mm, Shiseido);Flow rate: 1.0 ml/min; Mobile phase: acetonitrile/0.05M ammonium acetateaqueous solution (80:20), pH of the solvent was adjusted to 7.4 withaqueous ammonia or acetic acid.

1-276 (the enantiomer of 1-278):

[α]_(D) ²⁹=+7.41 (c 1.00, CH₃OH)

1-277 (the enantiomer of 1-279):

HPLC retention time: 6.0 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=8:1, flowrate: 1.0 mL/min.)

1-278 (the enantiomer of 1-276):

[α]_(D) ²⁹=−5.90 (c 1.01, CH₃OH)

1-279 (the enantiomer of 1-277):

HPLC retention time: 5.5 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=8:1, flowrate: 1.0 mL/min.)

1-280:

[α]_(D) ²⁹=−9.30 (c 0.41, CH₃OH)

1-281:

[α]_(D) ²⁸=−11.2 (c 0.41, CH₃OH)

1-282:

[α]_(D) ²⁸=−18.0 (c 0.41, CH₃OH)

1-283:

[α]_(D) ²²=−6.6 (c 0.40, CH₃OH)

1-284:

[α]_(D) ²⁸=−5.5 (c 0.40, CH₃OH)

1-302 (the enantiomer of 1-304):

HPLC retention time: 8.4 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=8:1, flowrate: 1.0 mL/min.)

1-303 (the Enantiomer of 1-305):

HPLC retention time: 9.2 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=8:1, flowrate: 1.0 mL/min.)

1-304 (the Enantiomer of 1-302):

HPLC retention time: 8.9 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=8:1, flowrate: 1.0 mL/min.)

1-305 (the Enantiomer of 1-303):

HPLC retention time: 10.6 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), 0.46 cm I.D.×25 cm, mobile phase: hexane/IPA=8:1, flowrate: 1.0 mL/min.)

1-306 (the Enantiomer of 1-308):

[α]_(D) ²⁸=+5.38 (c 0.81, CH₃OH)

1-307 (the Enantiomer of 1-309):

HPLC retention time: 16.6 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), (0.46 cm I.D.×25 cm)×2, mobile phase: hexane/IPA=8:1,flow rate: 1.0 mL/min.)

1-308 (the Enantiomer of 1-306):

[α]_(D) ²⁹=−7.69 (c 0.80, CH₃OH)

1-309 (the enantiomer of 1-307):

HPLC retention time: 17.4 min. (CHIRAL PAK AD (DAICEL CHEMICALINDUSTRIES, LTD), (0.46 cm I.D.×25 cm)×2, mobile phase: hexane/IPA=8:1,flow rate: 1.0 mL/min.)

1-316:

MS (ES, Pos.): 451 (M+1)⁺; HPLC retention time: 6.26 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

1-325:

MS (ES, Pos.): 449 (M+1)⁺; HPLC retention time: 5.78 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

1-338:

MS (ES, Pos.): 360 (M+1)⁺; HPLC retention time: 6.19 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

1-339:

MS (ES, Pos.): 424 (M+1)⁺, 426 (M+3)⁺; HPLC retention time: 5.93 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

*2: HCl salt*3: a mixture of diastereomers*4: optically active compound*5: Crystallized on standing from the compound purified (silica gelcolumn chromatography) and dried.

TABLE 2^(*) ¹

Com. No. Ex. No.

R¹⁰ R⁶ R⁷ R⁸ —Ar melting point (° C.) (solvent for crystallization)2-001 1

H CH₃ CH₃ CH₃

amorphous 2-002 1

H CH₃ CH₃ CH₃

amorphous 2-003 1

H CH₃ CH₃ H

119-121^(*2) (IPE) 2-004 1

H CH₃ CH₃ CH₃

200-202^(*2) (EtOAc) 2-005 1

H CH₃ CH₃ H

202-206^(*2) (ACE) 2-006 1

H CH₃ CH₃ CH₃

228-230^(*2) (EtOAc) 2-007 1

H CH₃ CH₃ H

218-220^(*2) (ACE) 2-008 1

H CH₃ CH₃ CH₃

179-181^(*2) (EtOAc/EtOH) 2-009 1

H CH₃ CH₃ H

204-206^(*2) (ACE) 2-010 1

H CH₃ CH₃ CH₃

146-148^(*2) (EtOAc/EtOH) 2-011 1

H CH₃ CH₃ H

108-110^(*2) (IPE) 2-012 1

H CH₃ CH₃ CH₃

amorphous 2-013 1

H CH₃ CH₃ CH₃

163-165^(*2) (EtOAc/EtOH) 2-014 1

H CH₃ CH₃ H

179-181^(*2) (ACE) 2-015 1

H CH₃ CH₃ CH₃

149-151^(*2) (EtOAc) 2-016 1

H CH₃ CH₃ CH₃

125-127^(*2) (MeOH/IPE) 2-017 1

H CH₃ CH₃ CH₃

172-174^(*2) (ACE/IPE) 2-018 1

H CH₃ CH₃ CH₃

133-135^(*2) (MeOH) 2-019 1

H CH₃ CH₃ H

207-209^(*2) (ACE) 2-020 1

H CH₃ CH₃ CH₃

130-132^(*2) (MeOH/IPE) 2-021 1

H CH₃ CH₃ CH₃

124-126^(*2) (MeOH) 2-022 1

H CH₃ CH₃ H

110-112^(*2) (IPE) 2-023 1

H CH₃ CH₃ CH₃

132-134^(*2) (MeOH/IPE) 2-024 1

H CH₃ CH₃ CH₃

130-132^(*2) (MeOH) 2-025 1

H CH₃ CH₃ H

200-202^(*2) (IPA) 2-026 1

H CH₃ CH₃ CH₃

122-124^(*2) (MeOH) 2-027 1

H CH₃ CH₃ CH₃

198-200^(*2) (MeOH/IPE) 2-028 1

H CH₃ CH₃ CH₃

124-126^(*2) (MeOH) 2-029 1

H CH₃ CH₃ H

184-186^(*2) (Et2O) 2-030 1

H CH₃ CH₃ CH₃

138-140^(*2) (MeOH) 2-031 1

H CH₃ CH₃ H

157-159^(*2) (ACE) 2-032 1

H CH₃ CH₃ H

154-156^(*2) (Et2O) 2-033 1

H CH₃ CH₃ CH₃

167-169^(*2) (MeOH) 2-034 1

H CH₃ CH₃ H

amorphous^(*2) 2-035 1

H CH₃ CH₃ CH₃

223-225^(*2) (ACE) 2-036 1

H CH₃ CH₃ H

236-238^(*2) (CH3CN) 2-037 1

H CH₃ CH₃ CH₃

228-230^(*2) (ACE) 2-038 1

H CH₃ CH₃ H

230-232^(*2) (CH3CN) 2-039 1

H CH₃ CH₃ CH₃

218-220^(*2) (ACE) 2-040 1

H CH₃ CH₃ H

232-234^(*2) (ACE) 2-041 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-042 1

H CH₃ CH₃ H

241-243^(*2) (CH3CN) 2-043 1

H CH₃ CH₃ CH₃

218-220^(*2) (ACE) 2-044 1

H CH₃ CH₃ H

182-184^(*2) (CH3CN) 2-045 1

H CH₃ CH₃ H

amorphous^(*2) 2-046 1

H CH₃ CH₃ H

amorphous^(*2) 2-047 1

H CH₃ CH₃ H

198-200^(*2) (CH3CN) 2-048 1

H CH₃ CH₃ H

amorphous^(*2) 2-049 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-050 1

H CH₃ CH₃ H

amorphous^(*2) 2-051 1

CO₂Et CH₃ CH₃ CH₃

169-171 (IPE) 2-052 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-053 1

H CH₃ CH₃ H

amorphous^(*2) 2-054 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-055 1

H CH₃ CH₃ H

215-217^(*2) (CH3CN) 2-056 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-057 1

H CH₃ CH₃ H

amorphous^(*2) 2-058 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-059 1

H CH₃ CH₃ H

amorphous^(*2) 2-060 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-061 1

H CH₃ CH₃ H

210-212^(*2) (CH3CN) 2-062 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-063 1

H CH₃ CH₃ H

amorphous^(*2) 2-064 1

H CH₃ CH₃ H

amorphous^(*2) 2-065 1

H CH₃ CH₃ H

amorphous^(*2) 2-066 1

H CH₃ CH₃ H

amorphous^(*2) 2-067 1

H CH₃ CH₃ H

113-115^(*2) (IPE) 2-068 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-069 1

H CH₃ CH₃ H

amorphous^(*2) 2-070 1

Br CH₃ CH₃ H

216-218^(*2) (EtOAc/EtOH) 2-071 1

H CH₃ CH₃ CH₃

127-129^(*2) (MeOH) 2-072 1

H CH₃ CH₃ H

amorphous^(*2) 2-073 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-074 1

H CH₃ CH₃ H

215-217^(*2) (CH3CN) 2-075 1

H CH₃ CH₃ CH₃

202-204^(*2) (ACE) 2-076 1

H CH₃ CH₃ H

197-199^(*2) (CH3CN) 2-077 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-078 1

H CH₃ CH₃ H

amorphous^(*2) 2-079 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-080 1

H CH₃ CH₃ H

212-214^(*2) (CH3CN) 2-081 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-082 1

H CH₃ CH₃ H

178-180^(*2) (CH3CN) 2-083 1

H CH₃ CH₃ H

amorphous^(*2) 2-084 1

H CH₃ CH₃ H

amorphous^(*2) 2-085 1

H CH₃ CH₃ H

201-203^(*2) (CH3CN) 2-086 1

H CH₃ CH₃ H

192-194^(*2) (IPE) 2-087 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-088 1

H CH₃ CH₃ H

amorphous^(*2) 2-089 1

H CH₃ CH₃ CH₃

153-155^(*2) (Et2O) 2-090 1

H CH₃ CH₃ H

215-217^(*2) (CH3CN) 2-091 1

H CH₃ CH₃ CH₃

208-210^(*2) (IPE) 2-092 1

H CH₃ CH₃ H

207-209^(*2) (CH3CN) 2-093 1

H CH₃ CH₃ CH₃

130-132^(*2) (MeOH) 2-094 1

H CH₃ CH₃ H

amorphous^(*2) 2-095 1

H CH₃ CH₃ CH₃

236-238^(*2) (ACE) 2-096 1

H CH₃ CH₃ H

226-228^(*2) (Et2O) 2-097 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-098 1

H CH₃ CH₃ H

225-227^(*2) (Et2O) 2-099 1

H CH₃ CH₃ CH₃

amorphous 2-100 1

H CH₃ CH₃ H

amorphous^(*2) 2-101 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-102 1

H CH₃ CH₃ H

amorphous^(*2) 2-103 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-104 1

H CH₃ CH₃ H

amorphous^(*2) 2-105 1

H CH₃ CH₃ H

amorphous^(*2) 2-106 1

H CH₃ CH₃ H

amorphous^(*2) 2-107 1

H CH₃ CH₃ H

amorphous^(*2) 2-108 1

H CH₃ CH₃ H

amorphous^(*2) 2-109 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-110 1

H CH₃ CH₃ H

amorphous^(*2) 2-111 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-112 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-113 1

H CH₃ CH₃ H

amorphous^(*2) 2-114 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-115 1

H CH₃ CH₃ H

217-219^(*2) (ACE) 2-116 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-117 1

H CH₃ CH₃ H

amorphous^(*2) 2-118 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-119 1

H CH₃ CH₃ H

amorphous^(*2) 2-120 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-121 1

H CH₃ CH₃ H

amorphous^(*2) 2-122 1

H CH₃ CH₃ CH₃

amorphous^(*2) 2-123 1

H CH₃ CH₃ H

amorphous^(*2) 2-124 1

H CH₃ CH₃ H

amorphous^(*2) 2-125 1

H CH₃ CH₃ H

amorphous^(*2) 2-126 1

H CH₃ CH₃ H

amorphous^(*2) 2-127 1

H CH₃ CH₃ H

212-214^(*2) (IPE) 2-128 1

H CH₃ CH₃ H

amorphous^(*2) 2-129 1

CO₂Et CH₃ CH₃ CH₃

176-178 (IPE) *1: Com. No. = compound number, Ex. No. = example number,solvent for crystallization; ACE = acetone, EtOAc = ethyl acetate, EtOH= ethanol, Et2O = diethylether, IPA = isopropyl alcohol, IPE =diisopropyl ether, MeOH = methanol, CH3CN = acetonitrile

Analytical data of non-crystal compounds are described below.

2-001:

MS (ES, Pos.): 418 (M+1)⁺, 420 (M+3)⁺, 422 (M+5)⁺

2-002:

MS (ES, Pos.): 432 (M+1)⁺, 434 (M+3)⁺, 436 (M+5)⁺

2-012:

MS (ES, Pos.): 427 (M+1)⁺

2-034:

MS (ES, Pos.): 534 (M+1)⁺, 536 (M+3)⁺, 538 (M+5)⁺; HPLC retention time:6.55 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-041:

MS (ES, Pos.): 540 (M+1)⁺, 542 (M+3)⁺, 544 (M+5)⁺; HPLC retention time:6.60 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-045:

MS (ES, Pos.): 456 (M+1)⁺, 458 (M+3)⁺; HPLC retention time: 6.72 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-046:

MS (ES, Pos.): 424 (M+1)⁺; HPLC retention time: 6.61 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-048:

MS (ES, Pos.): 482 (M+1)⁺, 484 (M+3)⁺; HPLC retention time: 5.67 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-049:

MS (ES, Pos.): 584 (M+1)⁺, 586 (M+3)⁺, 588 (M+5)⁺; HPLC retention time:6.73 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-050:

MS (ES, Pos.): 570 (M+1)⁺, 572 (M+3)⁺, 574 (M+5)⁺; HPLC retention time:6.90 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-052:

MS (ES, Pos.): 562 (M+1)⁺, 564 (M+3)⁺, 562 (M+5)⁺; HPLC retention time:6.81 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-053:

MS (ES, Pos.): 548 (M+1)⁺, 550 (M+3)⁺, 552 (M+5)⁺; HPLC retention time:6.72 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-054:

MS (ES, Pos.): 598 (M+1)⁺, 600 (M+3)⁺, 602 (M+5)⁺; HPLC retention time:6.47 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min andreequilibrate with 100% A for 1.5 min)

2-056:

MS (ES, Pos.): 510 (M+1)⁺, 512 (M+3)⁺, 514 (M+5)⁺; HPLC retention time:6.42 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-057:

MS (ES, Pos.): 496 (M+1)⁺, 498 (M+3)⁺, 500 (M+5)⁺; HPLC retention time:6.55 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-058:

MS (ES, Pos.): 466 (M+1)⁺, 468 (M+3)⁺, 470 (M+5)⁺; HPLC retention time:6.82 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-059:

MS (ES, Pos.): 452 (M+1)⁺, 454 (M+3)⁺, 456 (M+5)⁺; HPLC retention time:6.23 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-060:

MS (ES, Pos.): 554 (M+1)⁺, 556 (M+3)⁺, 558 (M+5)⁺; HPLC retention time:6.43 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-062:

MS (ES, Pos.): 422 (M+1)⁺; HPLC retention time: 6.29 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-063:

MS (ES, Pos.): 408 (M+1)⁺; HPLC retention time: 5.94 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-064:

MS (ES, Pos.): 470 (M+1)⁺, 472 (M+3)⁺, HPLC retention time: 6.92 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-065:

MS (ES, Pos.): 438 (M+1)⁺; HPLC retention time: 6.40 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-066:

MS (ES, Pos.): 506 (M+1)⁺, 508 (M+3)⁺, 510 (M+5)⁺; HPLC retention time:6.31 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-068:

MS (ES, Pos.): 598 (M+1)⁺, 600 (M+3)⁺, 602 (M+5)⁺; HPLC retention time:7.11 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-069:

MS (ES, Pos.): 584 (M+1)⁺, 586 (M+3)⁺, 588 (M+5)⁺; HPLC retention time:7.11 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 mL/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-072:

MS (ES, Pos.): 562 (M+1)⁺, 564 (M+3)⁺, 566 (M+5)⁺; HPLC retention time:6.63 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-073:

MS (ES, Pos.): 612 (M+1)⁺, 614 (M+3) % 616 (M+5)⁺; HPLC retention time:6.61 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-077:

MS (ES, Pos.): 480 (M+1)⁺, 482 (M+3)⁺, 484 (M+5)⁺; HPLC retention time:6.54 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-078:

MS (ES, Pos.): 466 (M+1)⁺, 468 (M+3)⁺, 470 (M+5)⁺; HPLC retention time:5.95 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-079:

MS (ES, Pos.): 568 (M+1)⁺, 570 (M+3)⁺, 572 (M+5)⁺; HPLC retention time:6.97 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-081:

MS (ES, Pos.): 436 (M+1)⁺; HPLC retention time: 6.49 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-083:

MS (ES, Pos.): 484 (M+1)⁺, 486 (M+3)⁺; HPLC retention time: 7.09 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-084:

MS (ES, Pos.): 452 (M+1)⁺; HPLC retention time: 6.55 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% Bin 1 min, 100% B for 1 min. and reequilibrate with100% A for 1.5 min)

2-087:

MS (ES, Pos.): 612 (M+1)⁺, 614 (M+3)⁺, 616 (M+5)⁺; HPLC retention time:7.24 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-088:

MS (ES, Pos.): 598 (M+1)⁺, 600 (M+3)⁺, 602 (M+5)⁺; HPLC retention time:7.21 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-094:

MS (ES, Pos.): 529 (M+1)⁺, 531 (M+3)⁺, 533 (M+5)⁺; HPLC retention time:6.40 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-097:

MS (ES, Pos.): 491 (M+1)⁺, 493 (M+3)⁺, 495 (M+5)⁺; HPLC retention time:6.78 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-099:

MS (ES, Pos.): 447 (M+1)⁺, 449 (M+3)⁺, 451 (M+5)⁺; HPLC retention time:6.73 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-100:

MS (ES, Pos.): 433 (M+1)⁺, 435 (M+3)⁺, 437 (M+5)⁺; HPLC retention time:5.70 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-101:

MS (ES, Pos.): 535 (M+1)⁺, 537 (M+3)⁺, 539 (M+5)⁺; HPLC retention time:6.72 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-102:

MS (ES, Pos.): 521 (M+1)⁺, 523 (M+3)⁺, 525 (M+5)⁺; HPLC retention time:6.27 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-103:

MS (ES, Pos.): 403 (M+1); HPLC retention time: 6.24 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-104:

MS (ES, Pos.): 389 (M+1)⁺; HPLC retention time: 5.89 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-105:

MS (ES, Pos.): 451 (M+1)⁺, 453 (M+3) % HPLC retention time: 6.87 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min, to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-106:

MS (ES, Pos.): 419 (M+1)⁺; HPLC retention time: 6.33 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-107:

MS (ES, Pos.): 487 (M+1)⁺, 489 (M+3)⁺, 491 (M+5)⁺; HPLC retention time:6.20 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-108:

MS (ES, Pos.): 477 (M+1)⁺, 479 (M+3)⁺, 481 (M+5)⁺; HPLC retention time:6.21 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-109:

MS (ES, Pos.): 579 (M+1)⁺, 581 (M+3)⁺, 583 (M+5)⁺; HPLC retention time:7.00 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-110:

MS (ES, Pos.): 565 (M+1)⁺, 567 (M+3)⁺, 569 (M+5)⁺; HPLC retention time:7.00 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-111:

MS (ES, Pos.): 421 (M+1)⁺, 423 (M+3)⁺; HPLC retention time: 6.84 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-112:

MS (ES, Pos.): 557 (M+1)⁺, 559 (M+3)⁺, 561 (M+5)⁺; HPLC retention time:6.54 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-113:

MS (ES, Pos.): 543 (M+1)⁺, 545 (M+3)⁺, 547 (M+5)⁺; HPLC retention time:6.69 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-114:

MS (ES, Pos.): 593 (M+1)⁺, 595 (M+3)⁺, 597 (M+5)⁺; HPLC retention time:6.84 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-116:

MS (ES, Pos.): 505 (M+1)⁺, 507 (M+3)⁺, 509 (M+5)⁺; HPLC retention time:6.37 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-117:

MS (ES, Pos.): 491 (M+1)⁺, 493 (M+3)⁺, 495 (M+5)⁺; HPLC retention time:6.52 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-118:

MS (ES, Pos.): 461 (M+1) % 463 (M+3)⁺, 465 (M+5)⁺; HPLC retention time:6.34 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-119:

MS (ES, Pos.): 447 (M+1)⁺, 449 (M+3)⁺, 451 (M+5)⁺; HPLC retention time:5.79 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-120:

MS (ES, Pos.): 549 (M+1)⁺, 551 (M+3)⁺, 553 (M+5)⁺; HPLC retention time:6.77 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-121:

MS (ES, Pos.): 535 (M+1)⁺, 537 (M+3)⁺, 539 (M+5)⁺; HPLC retention time:5.83 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-122:

MS (ES, Pos.): 417 (M+1)⁺; HPLC retention time: 6.49 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-123:

MS (ES, Pos.): 403 (M+1)⁺; HPLC retention time: 5.96 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-124:

MS (ES, Pos.): 465 (M+1)⁺, 467 (M+3)⁺, HPLC retention time: 6.87 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

2-125:

MS (ES, Pos.): 433 (M+1)⁺; HPLC retention time: 6.38 min. (Xterra MS C18(Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6 ml/min.Three mobile phases (mobile phase A 95% 25 mM ammonium acetate+5%acetonitrile; mobile phase B: acetonitrile; mobile phase C: methanol)were employed to run a gradient condition from 100% A to 50% B and 50% Cin 6.5 min., to 100% B in 1 min, 100% B for 1 min. and reequilibratewith 100% A for 1.5 min)

2-126:

MS (ES, Pos.): 501 (M+1)⁺, 503 (M+3)⁺, 505 (M+5)⁺; HPLC retention time:6.26 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

2-128:

MS (ES, Pos.): 579 (M+1)⁺, 581 (M+3)⁺, 583 (M+5)⁺; HPLC retention time:6.10 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

*2: HCl salt

Table3^(*1)

Com. No. Ex. No.

Y R⁶ R⁷ R⁸ —Ar melting point (° C.) (solvent for crystallization) 3-0015

N CH₃ CH₃ H

151-153 (No solvent) 3-002 5

CH CH₃ CH₃ H

amorphous 3-003 6

N CH₃ CH₃ H

142-144 (IPE) 3-004 6

N CH₃ CH₃ H

143-145 (IPE) 3-005 6

CH CH₃ CH₃ H

amorphous 3-006 6

N CH₃ CH₃ H

131-133 (hexane) 3-007 6

CH CH₃ CH₃ H

amorphous 3-008 5

N CH₃ CH₃ H

amorphous 3-009 6

N CH₃ CH₃ H

amorphous 3-010 6

CH CH₃ CH₃ CH₃

oil 3-011 6

CH CH₃ CH₃ H

oil 3-012 5

N CH₃ CH₃ H

110-112 (No solvent) 3-013 5

N CH₃ CH₃ CH₃

amorphous 3-014 8

N CH₃ CH₃ H

205-207^(*2) (No solvent) 3-015 7

N CH₃ CH₃ H

amorphous 3-016 8

N CH₃ CH₃ H

amorphous^(*2) 3-017 9

N CH₃ CH₃ H

94-96 (No solvent) 3-018 10 

N CH₃ CH₃ H

215-217^(*3) (No solvent) 3-019 7

N CH₃ CH₃ H

amorphous 3-020 7

N CH₃ CH₃ H

amorphous 3-021 7

N CH₃ CH₃ H

amorphous 3-022 7

N CH₃ CH₃ H

amorphous *1: Com. No. = compound number, Ex. No. = example number,solvent for crystallization; IPE = diisopropyl ether

Analytical data of non-crystal compounds are described below.

3-002:

MS (ES, Pos.): 514 (M+516 (M+3)⁺; HPLC Retention time: 6.77 min. (XterraMS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate 1.6ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

3-005:

MS (ES, Pos.): 547 (M+1)⁺, 549 (M+3)⁺; HPLC Retention time: 7.06 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

3-007:

MS (ES, Pos.): 514 (M+1) % 516 (M+3)⁺; HPLC Retention time: 7.01 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

3-008:

MS (ES, Pos.): 577 (M+1)⁺, 579 (M+3)⁺; HPLC Retention time: 10.89 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.2 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 30% A, 50% Band 20% C to 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for1 min. and reequilibrate with 100% A for 1.5 min)

3-009:

MS (ES, Pos.): 597 (M+1)⁺, 599 (M+3)⁺; HPLC Retention time: 13.94 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.2 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 30% A, 50% Band 20% C to 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for1 min. and reequilibrate with 100% A for 1.5 min)

3-010:

MS No spectrum (decomposition in LC-MS); ¹H NMR (360 MHz, DMSO-D6) 5 ppm0.83 (3H, t, J=6.4 Hz), 1.24 (12H, br.s), 1.52 (4H, m), 1.79 (9H, m),1.93 (3H, s), 2.29 (3H, s), 2.32 (2H, t, J=7.1 Hz), 2.39 (3H, s), 2.68(2H, t, J=11.3 Hz), 3.46 (2 H, d, J=11.7 Hz,), 4.00 (2H, d, J=5.9 Hz),6.45 (1H, s), 7.47 (2H, s)

3-011:

MS (ES, Pos.): 596 (M+1)⁺, 598 (M+3)⁺; HPLC Retention time: 6.45 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

3-013:

MS (ES, Pos.): 617 (M+1)⁺, 619 (M+3)⁺, 621 (M+5)⁺; HPLC Retention time:6.65 min. (Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm);Flow rate 1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mMammonium acetate+5% acetonitrile; mobile phase B: acetonitrile; mobilephase C: methanol) were employed to run a gradient condition from 100% Ato 50% B and 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min.and reequilibrate with 100% A for 1.5 min)

3-015:

MS (ES, Pos.): 570 (M+1)⁺, 572 (M+3)⁺; HPLC Retention time: 7.05 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

3-016:

MS (ES, Pos.): 629 (M+1)⁺, 631 (M+3)⁺; HPLC Retention time: 6.86 min.(Xterra MS C18 (Waters, Milford, Mass.) 3.5 μm, 4.6×100 mm); Flow rate1.6 ml/min. Three mobile phases (mobile phase A 95% 25 mM ammoniumacetate+5% acetonitrile; mobile phase B: acetonitrile; mobile phase C:methanol) were employed to run a gradient condition from 100% A to 50% Band 50% C in 6.5 min., to 100% B in 1 min, 100% B for 1 min. andreequilibrate with 100% A for 1.5 min)

3-019:

MS (ES, Pos.): 705 (M+1)⁺, 707 (M+3)⁺; NMR (300 MHz, CDCl₃) 8 ppm 0.89(3 H, t, J=6.7 Hz), 1.17-1.40 (14H, m), 1.42-1.72 (4H, m), 1.81-1.93(3H, m), 1.92 (6H, s), 2.00-2.07 (4H, m), 2.34 (2H, t, J=7.5 Hz), 2.44(3H, d, J=1.1 Hz), 2.51 (3H, s), 2.74-2.81 (2H, m), 2.90-3.04 (2H, m),4.03 (2H, d, J=6.4 Hz,), 4.10-4.19 (2H, m), 5.28-5.42 (4H, m), 6.57 (1H,m), 7.30 (2H, s)

3-020:

MS (ES, Pos.): 729 (M+1)⁺, 731 (M+3)⁺; ¹H NMR (300 MHz, CDCl₃) δ ppm0.89 (3 H, t, J=6.7 Hz), 1.20-1.40 (6H, m), 1.41-1.53 (2H, m), 1.65-1.80(2H, m), 1.81-2.00 (3H, m), 1.92 (6H, s), 2.02-2.19 (4H, m), 2.36 (2H,t, J=7.5 Hz), 2.44 (3H, d, J=1.0 Hz), 2.51 (3H, s), 2.77-2.90 (6H, m),2.92-3.05 (2H, m), 4.03 (2H, d, J=6.4 Hz,), 4.05-4.19 (2H, m), 5.28-5.47(8H, m), 6.57 (1H, m), 7.30 (2H, s)

3-021:

MS (ES, Pos.): 753 (M+1)⁺, 754 (M+3)⁺; ¹H NMR (500 MHz, CDCl₃) 8 ppm0.97 (3 H, t, J=7.3 Hz), 1.15-1.40 (1H, m), 1.45-1.55 (2H, m), 1.84-2.00(3H, m), 1.92 (6H, s), 2.04-2.11 (2H, m), 2.38-2.44 (4H, m), 2.43 (3H,d, J=1.2 Hz), 2.50 (3H, s), 2.77-2.90 (10H, m), 2.94-3.02 (2H, m), 4.04(2H, d, J=6.7 Hz,), 4.09-4.16 (2H, m), 5.27-5.46 (12H, m), 6.57 (1H, m),7.30 (2H, s)

3-022:

MS (ES, Pos.): 727 (M+1)⁺, 729 (M+3)⁺; ¹H NMR (500 MHz, CDCl₃) 8 ppm0.97 (3 H, t, J=7.3 Hz), 1.15-1.40 (1H, m), 1.45-1.55 (2H, m), 1.65-1.80(2H, m), 1.84-1.98 (2H, m), 1.92 (6H, s), 2.03-2.17 (4H, m), 2.36 (2H,t, J=7.3 Hz), 2.43 (3H, d, J=1.2 Hz), 2.50 (3H, s), 2.77-2.91 (8H, m),2.94-3.02 (2H, m), 4.04 (2H, d, J=6.7 Hz,), 4.09-4.16 (2H, m), 5.28-5.44(10H, m), 6.57 (1H, m), 7.30 (2H, s)

*2: optically active compound*3: 1 Na salt

Test Example CRF Receptor Binding Test

Monkey amygdala membranes were used as a receptor preparation.

¹²⁵I—CRF was used as ¹²⁵I-labeled ligand.

Binding reaction using the ¹²⁵I-labeled ligand was carried out by thefollowing method described in The Journal of Neuroscience, 7, 88 (1987).

Preparation of Receptor Membranes:

Monkey amygdala was homogenized in 50 mM Tris-HCl buffer (pH 7.0)containing 10 mM MgCl₂, 2 mM EDTA and centrifuged at 48,000×g for 20min, and the precipitate was washed once with Tris-HCl buffer. Thewashed precipitate was suspended in 50 mM Tris-HCl buffer (pH 7.0)containing 10 mM MgCl₂, 2 mM EDTA, 0.1% bovine serum albumin and 100kallikrein units/ml aprotinin, to obtain a membrane preparation.

CRF Receptor Binding Test:

The membrane preparation (0.3 mg protein/ml), ¹²⁵I—CRF (0.2 nM) and atest drug were reacted at 25° C. for 2 hours. After completion of thereaction, the reaction mixture was filtered by suction through a glassfilter (GF/C) treated with 0.3% polyethylene imine, and the glass filterwas washed three times with phosphate-buffered saline containing 0.01%Triton X-100. After the washing, the radioactivity of the filter paperwas measured in a gamma counter.

The amount of ¹²⁵I—CRF bound when the reaction was carried out in thepresence of 1 μM CRF was taken as the degree of nonspecific binding of¹²⁵I—CRF, and the difference between the total degree of ¹²⁵I—CRFbinding and the degree of nonspecific ¹²⁵I—CRF binding was taken as thedegree of specific ¹²⁵I—CRF binding. An inhibition curve was obtained byreacting a definite concentration (0.2 nM) of ¹²⁵I—CRF with variousconcentrations of each test drug under the conditions described above. Aconcentration of the test drug at which binding of ¹²⁵I—CRF is inhibitedby 50% (IC₅₀) was determined from the inhibition curve.

As a result, it was found that compounds 1-003, 1-004, 1-005, 1-007,1-008, 1-009, 1-010, 1-013, 1-014, 1-016, 1-018, 1-019, 1-021, 1-032,1-038, 1-039, 1-040, 1-046, 1-050, 1-051, 1-052, 1-053, 1-054, 1-056,1-057, 1-058, 1-059, 1-060, 1-061, 1-062, 1-063, 1-064, 1-067, 1-068,1-072, 1-073, 1-074, 1-077, 1-078, 1-087, 1-088, 1-089, 1-090, 1-091,1-097, 1-098, 1-099, 1-103, 1-104, 1-105, 1-112, 1-117, 1-118, 1-120,1-121, 1-122, 1-123, 1-125, 1-126, 1-127, 1-128, 1-129, 1-130, 1-131,1-132, 1-133, 1-135, 1-141, 1-142, 1-143, 1-144, 1-145, 1-148, 1-149,1-150, 1-151, 1-152, 1-153, 1-154, 1-155, 1-156, 1-157, 1-158, 1-159,1-160, 1-161, 1-162, 1-163, 1-164, 1-165, 1-166, 1-167, 1-172, 1-173,1-176, 1-177, 1-178, 1-179, 1-181, 1-183, 1-184, 1-188, 1-195, 1-208,1-213, 1-235, 1-236, 1-237, 1-243, 1-245, 1-251, 1-257, 1-262, 1-264,1-278, 1-280, 1-283, 1-284, 1-285, 1-286, 1-287, 1-288, 1-302, 1-304,1-306, 1-308, 1-319, 1-320, 1-332, 1-333, 1-336, 1-337, 2-002, 2-003,2-004, 2-005, 2-006, 2-007, 2-008, 2-009, 2-010, 2-011, 2-012, 2-013,2-014, 2-015, 2-016, 2-017, 2-018, 2-019, 2-020, 2-021, 2-022, 2-023,2-024, 2-025, 2-026, 2-027, 2-028, 2-029, 2-030, 2-031, 2-032, 2-033,2-034, 2-035, 2-036, 2-037, 2-038, 2-039, 2-040, 2-041, 2-042, 2-043,2-044, 2-045, 2-046, 2-047, 2-048, 2-049, 2-050, 2-052, 2-053, 2-054,2-055, 2-056, 2-057, 2-058, 2-059, 2-060, 2-061, 2-062, 2-063, 2-064,2-065, 2-066, 2-068, 2-069, 2-070, 2-071, 2-072, 2-073, 2-074, 2-075,2-076, 2-077, 2-078, 2-079, 2-080, 2-081, 2-082, 2-084, 2-087, 2-088,2-089, 2-090, 2-091, 2-092, 2-093, 2-094, 2-095, 2-096, 2-097, 2-098,2-099, 2-100, 2-101, 2-102, 2-103, 2-104, 2-105, 2-106, 2-107, 2-108,2-109, 2-110, 2-111, 2-112, 2-113, 2-114, 2-115, 2-116, 2-117, 2-118,2-119, 2-120, 2-121, 2-122, 2-123, 2-124, 2-125, 2-126, 2-127, 2-128,3-001, 3-004, 3-006, 3-007, 3-008, 3-009, 3-015 and 3-018 can beexemplified as typical compounds having an IC₅₀ value of 50 nM or less.

Effect of the Invention

According to the present invention, compounds having a high affinity forCRF receptors have been provided. These compounds are effective againstdiseases in which CRF is considered to be involved, such as depression,anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea,eating disorder, hypertension, gastric diseases, drug dependence,epilepsy, cerebral infarction, cerebral ischemia, cerebral edema,cephalic external wound, inflammation, immunity-related diseases,alopecia, irritable bowel syndrome, sleep disorders, epilepsy,dermatitides, schizophrenia, etc.

1. A pyrrolopyridine compound substituted with a cyclic amino grouprepresented by the following formula [I]:

(wherein the cyclic amino group is represented by the following formula[II]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—X, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;X is cyano, hydroxy or —OR⁹; Y is CR¹⁰; R¹ is hydrogen, hydroxy,C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R² is hydrogen orC₁₋₅alkyl; R³ is hydrogen, cyano, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl; m is an integer selected from 0, 1, 2, 3, 4 and 5; nis 0 or 1; with the proviso that when X is hydroxy or OR⁹, and n is 0,then m is an integer selected from 1, 2, 3, 4 and 5; R⁴ is hydrogen,hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl or C₁₋₅alkyl; R⁵ ishydrogen or C₁₋₅alkyl; R⁶ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy or—N(R¹¹)R¹²; R⁷ and R⁸ are the same or different, and independently arehydrogen, halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy, —N(R^(11a))R^(12a), —CO₂R¹³,cyano, nitro, C₁₋₅alkylthio, trifluoromethyl or trifluoromethoxy; or R⁷and R⁸ are taken together to form —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—; R⁹is C₁₋₂₄acyl, C₁₋₁₀alkoxycarbonyl, aryl-C₁₋₅alkyloxycarbonyl,—CO—O—CHR¹⁴—O—CO—R¹⁵, —P(═O)(OR^(14a))OR^(15a),—CO—(CH₂)_(p)—(CHR¹⁶)_(q)—NR¹⁷R¹⁸, arylcarbonyl or heteroarylcarbonyl,wherein each said acyl, aryl and heteroaryl is unsubstituted orsubstituted with C₁₋₅alkoxy, and C₁₋₂₄acyl optionally includes one tosix double bonds; R¹⁰ is hydrogen, C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹;Ar is aryl or heteroaryl which aryl or heteroaryl is unsubstituted orsubstituted with 1 or more substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio,C₁₋₅alkylsulfonyl, cyano, nitro, hydroxy, —CO₂R^(19a), —C(═O)R^(19a),—CONR^(11b)R^(12b), —OC(═O)R^(19a), —NR^(11b)CO₂R^(19a),—S(O)_(r)NR^(11b)R^(12b), hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy,trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy,methylenedioxy, ethylenedioxy and —N(R²⁰)R²¹; with the proviso that whenX is hydroxy, Y is N, and the cyclic amino group is 5-membered ring,then Ar is aryl or heteroaryl which aryl or heteroaryl is substitutedwith at least one of substituents which are selected from halogen andtrifluoromethyl; R¹¹ and R¹² are the same or different, andindependently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl orC₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11a) and R^(12a) are the same or different,and independently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl orC₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11b) and R^(12b) are the same or different,and independently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl orC₃₋₈cycloalkyl-C₁₋₅alkyl; R¹³ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl,C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl; R¹⁴ and R¹⁵ are the same ordifferent, and independently are hydrogen, C₁₋₅alkyl or aryl-C₁₋₅alkyl;R^(14a) and R^(15a) are the same or different, and independently arehydrogen, C₁₋₅alkyl or aryl-C₁₋₅alkyl; R¹⁶ is hydrogen, C₁₋₅alkyl, aryl,heteroaryl, aryl-C₁₋₅alkyl, heteroaryl-C₁₋₅alkyl, hydroxy-C₁₋₅alkyl,hydroxycarbonyl-C₁₋₅alkyl, hydroxyphenyl-C₁₋₅alkyl, C₁₋₅ alkoxy-C₁₋₅alkyl, amino-C₁₋₅alkyl, guanidino-C₁₋₅ alkyl, mercapto-C₁₋₅alkyl, C₁₋₅alkylthio-C₁₋₅ alkyl or aminocarbonyl-C₁₋₅ alkyl; R¹⁷ and R¹⁸ are thesame or different, and independently are hydrogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, C₁₋₁₀acyl, C₁₋₁₀alkoxycarbonylor aryl-C₁₋₅alkyloxycarbonyl; or R¹⁶ and R¹⁷ are taken together to form—CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂— or —CH₂CH₂CH₂CH₂—; p is an integer selectedfrom 0, 1, 2, 3, 4 and 5; q is 0 or 1; R¹⁹ is hydrogen or C₁₋₅alkyl;R^(19a) is hydrogen or C₁₋₅alkyl; r is 1 or 2; R²⁰ and R²¹ are the sameor different, and independently are hydrogen or C₁₋₅alkyl), individualisomers thereof, racemic or non-racemic mixtures of isomers thereof orN-oxide thereof, or pharmaceutically acceptable salts and hydratesthereof.
 2. The pyrrolopyridine compound substituted with the cyclicamino group according to claim 1, which is a compound represented by thefollowing formula [III]:

(wherein the cyclic amino group is represented by the following formula[IV]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(m)—CN, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;Y is CR¹⁰; R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl; R² is hydrogen or C₁₋₅alkyl; R³ is hydrogen, cyano,C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; m is an integerselected from 0, 1, 2, 3, 4 and 5; n is 0 or 1; R⁴ is hydrogen, hydroxy,hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl or C₁₋₅alkyl; R⁵ is hydrogenor C₁₋₅alkyl; R⁶ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy or—N(R¹¹)R¹²; R⁷ and R⁸ are the same or different, and independently arehydrogen, halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy, —N(R^(11a))R^(12a),CO₂R¹³,cyano, nitro, C₁₋₅alkylthio, trifluoromethyl or trifluoromethoxy; or R⁷and R⁸ are taken together to form —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—;R¹⁰ is hydrogen, C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹; Ar is aryl orheteroaryl which aryl or heteroaryl is unsubstituted or substituted with1 or more substituents, which are the same or different, selected fromthe group consisting of halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₂₋₅alkenyl,C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio, C₁₋₅alkylsulfonyl, cyano, nitro,hydroxy, —CO₂R^(19a); —C(═O)R^(19a), —CONR^(11b)R^(12b), —OC(═O)R^(19a),—NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹; R¹¹ and R¹² are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11a)and R^(12a) are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₄cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11b) andR^(12b) are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; R¹³ is hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,C₁₋₅alkoxy-C₁₋₅alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl; R¹⁹ ishydrogen or C₁₋₅alkyl; R^(19a) is hydrogen or C₁₋₅alkyl; r is 1 or 2;R²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₅alkyl), individual isomers thereof or racemic or non-racemicmixtures of isomers thereof, or pharmaceutically acceptable salts andhydrates thereof.
 3. The pyrrolopyridine compound substituted with thecyclic amino group according to claim 2 represented by formula [III],wherein n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R¹⁰ is hydrogen orhalogen; and the cyclic amino group, m, R⁶, R⁷, R⁸ and Ar are as definedin claim 2; individual isomers thereof or racemic or non-racemicmixtures of isomers thereof, or pharmaceutically acceptable salts andhydrates thereof.
 4. The pyrrolopyridine compound substituted with thecyclic amino group according to claim 2 represented by formula [III],wherein the cyclic amino group is a 4- to 7-membered saturated cyclicamine; m is an integer selected from 0, 1, 2 and 3; n is 0; R¹, R², R⁴and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different,and independently are hydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen;and Ar is phenyl or pyridyl which phenyl or pyridyl is substituted withtwo or three substituents, which are the same or different, selectedfrom the group consisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy,C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (whereinR²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₃alkyl); individual isomers thereof or racemic or non-racemicmixtures of isomers thereof, or pharmaceutically acceptable salts andhydrates thereof.
 5. The pyrrolopyridine compound substituted with thecyclic amino group according to claim 2 represented by formula [III],wherein the cyclic amino group is a 6-membered saturated cyclic amine; mis 0 or 1; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ andR⁸ are the same or different, and independently are hydrogen or methyl;R¹⁰ is hydrogen; and Ar is phenyl which phenyl is substituted with twoor three substituents, which are the same or different, selected fromthe group consisting of chloro, bromo, C₁₋₃alkyl, C₁₋₃alkoxy,C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxy and dimethylamino;individual isomers thereof or racemic or non-racemic mixtures of isomersthereof, or pharmaceutically acceptable salts and hydrates thereof. 6.The pyrrolopyridine compound substituted with the cyclic, amino groupaccording to claim 1, which is a compound represented by the followingformula [V]:

(wherein the cyclic amino group is represented by the following formula[VI]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OH, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;Y is CR¹⁰; R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl; R² is hydrogen or C₁₋₅alkyl; R³ is hydrogen, cyano,C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; m is an integerselected from 0, 1, 2, 3, 4 and 5; n is 0 or 1; with the proviso thatwhen n is 0, m is an integer selected from 1, 2, 3, 4 and 5; R⁴ ishydrogen, hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl orC₁₋₅alkyl; R⁵ is hydrogen or C₁₋₅alkyl; R⁶ is hydrogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy, C₁₋₅alkoxy,C₃₋₈cycloalkyloxy or —N(R¹¹)R¹²; R⁷ and R⁸ are the same or different,and independently are hydrogen, halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy,—N(R^(11a))R^(12a), —CO₂R¹³, cyano, nitro, C₁₋₅alkylthio,trifluoromethyl or trifluoromethoxy; or R⁷ and R⁸ are taken together toform —CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—; R¹⁰ is hydrogen, C₁₋₅alkyl,halogen, cyano or —CO₂R¹⁹; Ar is aryl or heteroaryl which aryl orheteroaryl is unsubstituted or substituted with 1 or more substituents,which are the same or different, selected from the group consisting ofhalogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₂₋₅alkenyl, C₂₋₅alkynyl,C₁₋₅alkoxy, C₁₋₅alkylthio, C₁₋₅alkylsulfinyl, C₁₋₅alkylsulfonyl, cyano,nitro, hydroxy, —CO₂R^(19a), —C(═O)R^(19a), —CONR^(11b)R^(12b),—OC(═O)R^(19a), —NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹; with the proviso that when Y is N, and the cyclic aminogroup is 5-membered ring, then Ar is aryl or heteroaryl which aryl orheteroaryl is substituted with at least one of substituents which areselected from halogen and trifluoromethyl; R¹¹ and R¹² are the same ordifferent, and independently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl orC₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11a) and R^(12a) are the same or different,and independently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl orC₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11b) and R^(12b) are the same or different,and independently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl orC₃₋₈cycloalkyl-C₁₋₅alkyl; R¹³ is hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl; R¹⁹ ishydrogen or C₁₋₅alkyl; R^(19a) is hydrogen or C₁₋₅alkyl; r is 1 or 2;R²⁰ and R²¹ are the same or different, and independently are hydrogen orC₁₋₅alkyl), individual isomers thereof or racemic or non-racemicmixtures of isomers thereof, or pharmaceutically acceptable salts andhydrates thereof.
 7. The pyrrolopyridine compound substituted with thecyclic amino group according to claim 6 represented by formula [V],wherein m is an integer selected from 1, 2, 3, 4 and 5; n is 0; R¹, R²,R⁴ and R⁵ are hydrogen; R¹⁰ is hydrogen or halogen; and the cyclic aminogroup, R⁶, R⁷, R⁸ and Ar are as defined in claim 6; individual isomersthereof or racemic or non-racemic mixtures of isomers thereof, orpharmaceutically acceptable salts and hydrates thereof.
 8. Thepyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 6 represented by formula [V], wherein the cyclicamino group is a 4- to 7-membered saturated cyclic amine; m is aninteger selected from 1, 2 and 3; n is 0; R¹, R², R⁴ and R⁵ arehydrogen; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen; andAr is phenyl or pyridyl which phenyl or pyridyl is substituted with twoor three substituents, which are the same or different, selected fromthe group consisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰) R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl);individual isomers thereof or racemic or non-racemic mixtures of isomersthereof, or pharmaceutically acceptable salts and hydrates thereof. 9.The pyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 6 represented by formula [V], wherein the cyclicamino group is a 6-membered saturated cyclic amine; m is an integerselected from 1, 2 and 3; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R⁶ ismethyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or methyl; R¹⁰ is hydrogen; and Ar is phenyl which phenyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of chloro, bromo,C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxyand dimethylamino; individual isomers thereof or racemic or non-racemicmixtures of isomers thereof, or pharmaceutically acceptable salts andhydrates thereof.
 10. The pyrrolopyridine compound substituted with thecyclic amino group according to claim 6 represented by formula [V],wherein m is 1; n is 0; R¹ is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ andR⁵ are hydrogen; R¹⁰ is hydrogen or halogen; and the cyclic amino group,R⁶, R⁷, R⁸ and Ar are as defined in claim 6; individual isomers thereofor racemic or non-racemic mixtures of isomers thereof, orpharmaceutically acceptable salts and hydrates thereof.
 11. Thepyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 6 represented by formula [V], wherein m is 1; n is 0;the cyclic amino group is a 4- to 7-membered saturated cyclic amine; R¹is C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ and R⁵ are hydrogen; R⁶ ismethyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen; and Ar is phenyl orpyridyl which phenyl or pyridyl is substituted with two or threesubstituents, which are the same or different, selected from the groupconsisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl);individual isomers thereof or racemic or non-racemic mixtures of isomersthereof, or pharmaceutically acceptable salts and hydrates thereof. 12.The pyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 6 represented by formula [V], wherein m is 1; n is 0;the cyclic amino group is a 6-membered saturated cyclic amine; R¹ isC₁₋₅alkyl or hydroxy-C₁₋₅alkyl; R², R⁴ and R⁵ are hydrogen; R⁶ ismethyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or methyl; R¹⁰ is hydrogen; and Ar is phenyl which phenyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of chloro, bromo,C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxyand dimethylamino; individual isomers thereof or racemic or non-racemicmixtures of isomers thereof, or pharmaceutically acceptable salts andhydrates thereof.
 13. The pyrrolopyridine compound substituted with thecyclic amino group according to claim 6 represented by formula [V],wherein m is an integer selected from 1, 2, 3, 4 and 5; n is 0; R¹, R²and R⁵ are hydrogen; R⁴ is cyano; R¹⁰ is hydrogen or halogen; and thecyclic amino group, R⁶, R⁷, R⁸ and Ar are as defined in claim 6, whereina group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substitutedon the same carbon atom of the cyclic amine; individual isomers thereofor racemic or non-racemic mixtures of isomers thereof, orpharmaceutically acceptable salts and hydrates thereof.
 14. Thepyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 6 represented by formula [V], wherein the cyclicamino group is a 4- to 7-membered saturated cyclic amine; m is aninteger selected from 1, 2 and 3; n is 0; R¹, R² and R⁵ are hydrogen; R⁴is cyano; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or C₁₋₅alkyl; R¹⁰ is hydrogen or halogen; andAr is phenyl or pyridyl which phenyl or pyridyl is substituted with twoor three substituents, which are the same or different, selected fromthe group consisting of halogen, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio,trifluoromethyl, trifluoromethoxy and —N(R²⁰)R²¹ (wherein R²⁰ and R²¹are the same or different, and independently are hydrogen or C₁₋₃alkyl),wherein a group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ aresubstituted on the same carbon atom of the cyclic amine; individualisomers thereof or racemic or non-racemic mixtures of isomers thereof,or pharmaceutically acceptable salts and hydrates thereof.
 15. Thepyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 6 represented by formula [V], wherein the cyclicamino group is a 6-membered saturated cyclic amine; m is an integerselected from 1, 2 and 3; n is 0; R¹, R² and R⁵ are hydrogen; R⁴ iscyano; R⁶ is methyl; R⁷ and R⁸ are the same or different, andindependently are hydrogen or methyl; R¹⁰ is hydrogen; and Ar is phenylwhich phenyl is substituted with two or three substituents, which arethe same or different, selected from the group consisting of chloro,bromo, C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl,trifluoromethoxy and dimethylamino, wherein a group represented by—(CR¹R²)_(m)—(CHR³)_(n)—OH and R⁴ are substituted on the same carbonatom of the cyclic amine; individual isomers thereof or racemic ornon-racemic mixtures of isomers thereof, or pharmaceutically acceptablesalts and hydrates thereof.
 16. The pyrrolopyridine compound substitutedwith the cyclic amino group according to claim 1, which is a compoundrepresented by the following formula [VII]:

(wherein the cyclic amino group is represented by the following formula[VIII]:

in which the cyclic amino group is a 3- to 8-membered saturated cyclicamine or a 3- to 8-membered saturated cyclic amine bridged withC₁₋₅alkylene or C₁₋₄alkylene-O—C₁₋₄alkylene between any different twocarbon atoms of the cyclic amine, which cyclic amine is substituted witha group represented by —(CR¹R²)_(m)—(CHR³)_(n)—OR⁹, R⁴ and R⁵independently on the same or different carbon atoms of the cyclic amine;Y is CR¹⁰; R¹ is hydrogen, hydroxy, C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl orhydroxy-C₁₋₅alkyl; R² is hydrogen or C₁₋₅alkyl; R³ is hydrogen, cyano,C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl or hydroxy-C₁₋₅alkyl; m is an integerselected from 0, 1, 2, 3, 4 and 5; n is 0 or 1; with the proviso thatwhen n is 0, m is an integer selected from 1, 2, 3, 4 and 5; R⁴ ishydrogen, hydroxy, hydroxy-C₁₋₅alkyl, cyano, cyano-C₁₋₅alkyl orC₁₋₅alkyl; R⁵ is hydrogen or C₁₋₅alkyl; R⁶ is hydrogen, C₁₋₅alkyl,C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy, C₁₋₅alkoxy,C₃₋₈cycloalkyloxy or —N(R¹¹)R¹²; R⁷ and R⁸ are the same or different,and independently are hydrogen, halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, hydroxy, C₁₋₅alkoxy, C₃₋₈cycloalkyloxy,—N(R^(11a))R^(12a),CO₂R¹³, cyano, nitro, C₁₋₅alkylthio, trifluoromethylor trifluoromethoxy; or R⁷ and R⁸ are taken together to form—CH₂—CH₂—CH₂—CH₂— or —CH═CH—CH═CH—; R⁹ is C₁₋₂₄acyl,C₁₋₁₀alkoxycarbonyl, aryl-C₁₋₅alkyloxycarbonyl, —CO—O—CHR¹⁴—O—CO—R¹⁵,—P(═O)(OR^(14a))OR^(15a), —CO—(CH₂)_(p)—(CHR¹⁶)_(q)—NR¹⁷R¹⁸,arylcarbonyl or heteroarylcarbonyl, wherein each said acyl, aryl andheteroaryl is unsubstituted or substituted with C₁₋₅alkoxy, andC₁₋₂₄acyl optionally includes one to six double bonds; R¹⁰ is hydrogen,C₁₋₅alkyl, halogen, cyano or —CO₂R¹⁹; Ar is aryl or heteroaryl whicharyl or heteroaryl is unsubstituted or substituted with 1 or moresubstituents, which are the same or different, selected from the groupconsisting of halogen, C₁₋₅alkyl, C₃₋₈cycloalkyl, C₂₋₅alkenyl,C₂₋₅alkynyl, C₁₋₅alkoxy, C₁₋₅alkylthio, C₁₋₅alkylsulfonyl, cyano, nitro,hydroxy, —CO₂R^(19a), —C(═O)R^(19a), —CONR^(11b)R^(12b), —OC(═O)R^(19a),—NR^(11b)CO₂R^(19a), —S(O)_(r)NR^(11b)R^(12b),hydroxy-C₂₋₅alkylamino-C₂₋₅alkoxy, trifluoromethyl, trifluoromethoxy,difluoromethoxy, fluoromethoxy, methylenedioxy, ethylenedioxy and—N(R²⁰)R²¹; R¹¹ and R¹² are the same or different, and independently arehydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11a)and R^(12a) are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; R^(11b) andR^(12b) are the same or different, and independently are hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl or C₃₋₈cycloalkyl-C₁₋₅alkyl; R¹³ is hydrogen,C₁₋₅alkyl, C₃₋₈cycloalkyl, C₃₋₈cycloalkyl-C₁₋₅alkyl,C₁₋₅alkoxy-C₁₋₅alkyl, C₃₋₈cycloalkyloxy-C₁₋₅alkyl or phenyl; R¹⁴ and R¹⁵are the same or different, and independently are hydrogen, C₁₋₅alkyl oraryl-C₁₋₅alkyl; R^(14a) and R^(15a) are the same or different, andindependently are hydrogen, C₁₋₅alkyl or aryl-C₁₋₅alkyl; R¹⁶ ishydrogen, C₁₋₅alkyl, aryl, heteroaryl, aryl-C₁₋₅alkyl,heteroaryl-C₁₋₅alkyl, hydroxy-C₁₋₅alkyl, hydroxycarbonyl-C₁₋₅ alkyl,hydroxyphenyl-C₁₋₅alkyl, C₁₋₅alkoxy-C₁₋₅alkyl, amino-C₁₋₅alkyl,guanidino-C₁₋₅alkyl, mercapto-C₁₋₅alkyl, C₁₋₅alkyl oraminocarbonyl-C₁₋₅alkyl; R¹⁷ and R¹⁸ are the same or different, andindependently are hydrogen, C₁₋₅alkyl, C₃₋₈cycloalkyl,C₃₋₈cycloalkyl-C₁₋₅alkyl, C₁₋₁₀acyl, C₁₋₁₀alkoxycarbonyl andaryl-C₁₋₅alkyloxycarbonyl, or R¹⁶ and R¹⁷ are taken together to form—CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂— or —CH₂CH₂CH₂CH₂—; p is an integer selectedfrom 0, 1, 2, 3, 4 and 5; q is 0 or 1; R¹⁹ is hydrogen or C₁₋₅alkyl;R^(19a) is hydrogen or C₁₋₅alkyl; r is 1 or 2; R²⁰ and R²¹ are the sameor different, and independently are hydrogen or C₁₋₅alkyl), individualisomers thereof or racemic or non-racemic mixtures of isomers thereof,or pharmaceutically acceptable salts and hydrates thereof.
 17. Thepyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 16 represented by formula [VII], wherein m is aninteger selected from 1, 2, 3, 4 and 5; n is 0; R¹, R², R⁴ and a R⁵ arehydrogen; and the cyclic amino group, R⁶, R⁷, R⁸, R⁹, R¹⁰ and Ar are asdefined in claim 16; individual isomers thereof or racemic ornon-racemic mixtures of isomers thereof, or pharmaceutically acceptablesalts and hydrates thereof.
 18. The pyrrolopyridine compound substitutedwith the cyclic amino group according to claim 16 represented by formula[VII], wherein the cyclic amino group is a 4- to 7-membered saturatedcyclic amine; m is an integer selected from 1, 2 and 3; n is 0; R¹, R²,R⁴ and R⁵ are hydrogen; R⁶ is methyl; R⁷ and R⁸ are the same ordifferent, and independently are hydrogen or C₁₋₅alkyl; R¹⁰ is hydrogenor halogen; and Ar is phenyl or pyridyl which phenyl or pyridyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of halogen, C₁₋₃alkyl,C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxy and—N(R²⁰)R²¹ (wherein R²⁰ and R²¹ are the same or different, andindependently are hydrogen or C₁₋₃alkyl); R⁹ is as defined in claim 16;individual isomers thereof or racemic or non-racemic mixtures of isomersthereof, or pharmaceutically acceptable salts and hydrates thereof. 19.The pyrrolopyridine compound substituted with the cyclic amino groupaccording to claim 16 represented by formula [VII], wherein the cyclicamino group is a 6-membered saturated cyclic amine; m is an integerselected from 1, 2 and 3; n is 0; R¹, R², R⁴ and R⁵ are hydrogen; R⁶ ismethyl; R⁷ and R⁸ are the same or different, and independently arehydrogen or methyl; R¹⁰ is hydrogen; and Ar is phenyl which phenyl issubstituted with two or three substituents, which are the same ordifferent, selected from the group consisting of chloro, bromo,C₁₋₃alkyl, C₁₋₃alkoxy, C₁₋₃alkylthio, trifluoromethyl, trifluoromethoxyand dimethylamino; R⁹ is as defined in claim 16; individual isomersthereof or racemic or non-racemic mixtures of isomers thereof, orpharmaceutically acceptable salts and hydrates thereof.
 20. Thepyrrolopyridine compound represented by formula [I] according to claim1, which compound is selected from the group consisting of2-{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-ethanol,2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-ethanol,{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,2-{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,3-{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-3-carbonitrile,1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-3-carbonitrile,{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-acetonitrile,1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,{1-[1-(2,4-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-3-yl}-ethanol,{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,2-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,3-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-3-carbonitrile,1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(2,6-dibromo-4-chloro-phenyl)-3-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[1-(2-bromo-4-trifluoromethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,{1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-methanol,2-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl}-piperidin-4-yl]-ethanol,2-{1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[2,3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,2-{1-[5-bromo-1-(4-chloro-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethanol,3-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,3-{1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propan-1-ol,1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethane-1,2-diol,1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-ethane-1,2-diol,1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propane-1,3-diol,1-{1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-propane-1,3-diol,1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[1-(2-bromo-4-trifluoromethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[2,3,6-trimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidine-4-carbonitrile,{1-[1-(4-chloro-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2,6-dibromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[2,3,6-trimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[3,6-dimethyl-1-(2,4,6-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-bromo-2,6-dichloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-bromo-2,6-dichloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[2,3,6-trimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[3,6-dimethyl-1-(2,4,6-trichloro-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2,6-dibromo-4-chloro-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2,6-dibromo-4-chloro-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-2,3,6-trimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-methoxy-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2-bromo-4-isopropyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(4-isopropyl-2-methylsulfanyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2,4-dibromo-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[1-(2-bromo-4-trifluoromethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,{1-[3,6-dimethyl-1-(2,4,5-tribromo-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile,and methoxy-acetic acid1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-ylmethylester, individual isomers thereof or racemic or non-racemic mixtures ofisomers thereof, or pharmaceutically acceptable salts and hydratesthereof.
 21. A pharmaceutical composition comprising the pyrrolopyridinecompound substituted with a cyclic amino group, a pharmaceuticallyacceptable salt thereof or its hydrate according to claim 1, as anactive ingredient, and a pharmaceutically acceptable carrier.
 22. Amethod for the treatment of CRF related diseases in a mammal, saidmethod comprising the step of administering to said mammal an effectiveamount of the pyrrolopyridine derivative substituted with a cyclic aminogroup, a pharmaceutically acceptable salt thereof or its hydrateaccording to claim 1.